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V

Welcome Dear Students,

Welcome to the second year medicine. As you have already started in

the Faculty curriculum (System- Based Curriculum), this year you are in

Phase II of the program.

Phase I : Premedical Year (First Year)

Phase II : Second and Third Years

Phase III : Fourth, Fifth and Sixth Years

Congratulations, you passed phase I. But what about phase II? Phase II

includes many core modules and also System-Based Modules. The aim of

this phase is to lay down a solid foundation for the subsequent full-time

clinical study in stage III of the MBBS program. It will also integrate the

basic sciences knowledge with the clinical sciences. This include knowledge,

skill and attitudes, particularly attitudes towards the learning process. The

curriculum philosophy in stage II is enforcing the development of a mixture

of teaching approaches including System-Based Learning, Problem-Based

Learning and also stressing on the idea of "Student Self-Directed Learning".

The department has the honor to introduce this study guide to you

hoping that it may be helpful in making you oriented with the aims,

objectives, contents of our courses, and through it, you will find the answers

of the frequently asked questions.

All the Best

Department Chairman

VII

TABLE OF CONTENTS

TOPIC

Page

INTRODUCTION

COURSE DESCRIPTION AND ORGANIZATION

MAJOR COURSE OBJECTIVES

STUDY STRATEGIES AND CLASS PARTICIPATION EXPECTATIONS

INSTRUCTIONAL METHODS

ASSESSMENT & EVALUATION

TIME ALLOCATION

CLINICAL BIOCHEMISTRY DEPARTMENT STAFF LISTING

DEPARTMENT WEB SITE

ICONS

TOPIC OUTLINES

NO. LECTURES (NAMES)

01

02

03

04

05

06

07

08

VIII

09

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

IX

NO. PRACTICAL (Names)

01

02

03

04

05

06

07

08

09

10

11

12

13

14

TUTORIALS

01 Anatomy of the Heart and Big Vessels

02

03

04

05

07

08

09

10

1

Introduction

Welcome to the Department of Clinical Biochemistry. The aim of this

course guide is to provide you with clear description of the course objectives,

contents of each topic together with its lectures, tutorials and practicals, which

are presented in a sequential manner. Also it states clearly what is expected from

you to achieve together with the evaluation procedures. There is no reason to

suppose that Biochemistry is intrinsically uninteresting, difficult to understand or

an obstacle to be overcome during your progress to a professional qualifications.

In the contrary you can enjoy its study if you remember the simple biological

principals that the body is formed from organs and tissues and these are formed

from aggregates of cells. The cell is build up from sub-cellular structures which

by itself is an aggregate of molecules. Every human actively, like walking,

breathing and even thinking are the result of the interactions of these molecules.

Defective molecular processes result in disease state. Moreover Biochemistry has

become a background subject for a great family of medical sciences.

Understanding Biochemistry will build for you a good foundation for

understanding disease states, their prevention, diagnosis and treatment. We

advice you to read the objectives of each topic before the start of its lectures and

focus your attention on the important points. Take another look after the end of

the lecture to make sure that these points have been understood.

Dr. Zainy Mohammed Abdullah Banjar

Chairman, Department of Clinical Biochemistry

Faculty of Medicine Biochemical Basis of Medicine I

2

COURSE DESCRIPTION AND ORGANIZATION

The aim of Clinical Biochemistry II course for second year student is to

introduce you to the basic concepts of structure and metabolism in relation to

the mechanisms by which primary foodstuffs, proteins, carbohydrates and

lipids, are manipulated by the body in order to provide energy and to allow for

biosynthesis of cellular material. Also you will have a good view of storage,

transmission and expression of genetic information. Clinically relevant

examples will be discussed.

Biochemical basis of medicine I course includes and covers the following

topics: allosteric proteins, enzymes, membrane and transport, bioenergetics

and oxidative metabolism, anaerobic metabolism, tricarboxylic acid cycle,

carbohydrate storage and synthesis in liver and muscle, oxidative metabolism

of lipid in liver and muscle, biosynthesis and storage of fatty acids, lipid and

lipoproteins, and cholesterol metabolism.

The course consists of lectures, practical classes and tutorials.

Course Units

Core Course

Code/No

Lectures Practical Tutorial

Credit Hours

Biochemical Basis

Of Medicine I

30 15 15 3


3

MAJOR COURSE OBJECTIVES

On completion of the course in Clinical Biochemistry I student will:

1. Evaluate the biochemical logic of the human cell.

2. Explain the maintenance of cellular life in the term of energy

production and biosynthetic ability.

3. Apply biochemical knowledge to solve problems of human health and

disease.

4. Practice basic skills in applying laboratory techniques encountered in

hospital's clinical biochemistry laboratories.

5. Appreciate the functional role of membrane proteins as pumps, gates

and channels


4

STUDY STRATEGIES AND CLASS PARTICIPATION

EXPECTATIONS

The course offered to 2nd year medical students in clinical biochemistry consists of

scheduled lectures, tutorials and practicals which ensure smooth flow of the scientific material,

in a controlled manner, through several pathways to achieve our objectives. There is some

suggestion for optimal utilization of these classes by the students.

A. Lectures: The aim of the lecture is not to give information but to frame up the subject,

pointing out its relation to other parts of the course, its relevance to clinical situations and

to explain difficult points. To prepare your self for the lecture:

1. Give a thorough look to the course objectives and the topic outline delivered by the

department and try to read the topic from the recommended textbook.

2. Note taking in lectures keeps the student in track during studying the subject.

3. If is recommended to study the topic of the lecture, if possible, in the same day, to

prevent fading of knowledge. You can utilize different ways of self-testing in order

to assess your grasping of the subject.

B. Practicals: For optimal utilization of the practical class time it is advisable to:

1. Read your practical worksheet so as to have view of what is expected from you to

perform, observe and draw conclusions on your practical work.

2. A record of the practicals should be used according to instructions.

3. The practical time can also be used for discussing difficult theoretical or practical

points with the instructor.

C. Tutorials: For optimal benefit of the tutorial, the tutorial will be reserved for open

discussion about the subjects listed in the tutorial schedule. The students will be

assigned these topics and will be asked to present them and be ready to change the most

recent knowledge about these topics and how to defend their thoughts on scientific

bases


5

Instructional Methods

The main instructional material includes lectures, practicals to steamline the applied and

clinical aspects of the lectures and tutorials session to stimulate the students to participate

in the teaching/learning activities.

Instructional Materials And Resources

1. Required Texts And Resources

a. Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey

b. Baynes, Medical Biochemistry, Mosby, London.

2. Supplementary Texts And Resources

a. Thomas M. Devlin, Textbook of Biochemistry with Clinical Correlations, Jon

Willey & sons, New York.

b. Lubert Stryer, Biochemistry, W.H. Freeman and Company, San Francisco.

c. Pamela C. Champe, Biochemistry, Lippincott Raven.


6

ASSESSMENT

1. Formative:

This form of assessment is designed to give you feedback to help you to identify areas for

improvement. It includes a mixture of MCQs, short answer-questions (SAQs), extended

matching questions (EMQs), problems-solving exercises and independent learning

activities in all subjects. These will be given during tutorial sessions and practicals. The

Answers are presented and discussed immediately with you after the assessment. The

results will be made available to you.

2. Summative

This type of assessment is used for judgment or decisions to be made about your performance.

It serves as:

a. Verification of achievement for the student satisfying requirement

b. Motivation of the student to maintain or improve performance

c. Certification of performance

d. Grades

In this Course your performance will be assessed according to the following:

1. Continuous Assessment 20 Marks

2. Assignment 20 Marks

3. OSPE 20 Marks

4. Final End of Semester Exam (Two Hours) 40 Marks

Total = 100 Marks


7

All grades will be assigned as follows:

Exams: Exams will include short answer and multiple choice questions (MCQs). They will

cover material presented in lecture, readings, and discussion. All exams must be taken on the

date scheduled. In case of an emergency, the coordinator must be notified. No make-up exams

will be provided if you fail to notify and discuss your situation with the coordinator.

Assignment paper: The purpose of the work is to provide you with the opportunity to explore

an area of basic medical sciences or medical education in depth. The paper is to be a 10-15

page literature review of the topic will constitute 20% of your final grade. Policy: Topics must

be approved in writing by the coordinator. Directions for topic submission will be discussed

during the first week of class. Topics that have not been approved will not be accepted.

All papers must reference a minimum of eight references from refereed journals. All papers

must be typed, double-spaced, have 1 inch margins.

Note: We will be making the journey from "womb to tomb" in 15 weeks. Therefore, this

course requires an intensive coursework load. Class attendance and participation are extremely

important to your learning and as such are considered in the evaluation of your course grade.

This course is recommended for students that can make the required time and energy

commitment. If there is anything that the coordinator can do to assist you during the course,

please feel free to contact him.

85 - 100 A Excellent

75 - 84 B Very good

65 - 74 C Good

60 - 64 D Pass

Less than 60 F Fail


8

Time Allocations

BIOCHEMICAL BASIS OF MEDICINE

Topic Lecture Practical Tutorial

BIOCHEMICAL BASIS OF MEDICINE I:

1. Allosteric proteins 3 1 1

2. Collagen 1

3. Catalytic proteins - Enzymes 7 3 4

3. Membrane and transport 2

4- Cellular transduction 1

5. Introduction to Metabolism, Bioenergetics, 2 1 1

and the Role of ATP

6. Glycolysis 2 1 1

7. The tricarboxylic acid cycle 1 1 1

8. Gluconeogenesis 1 1 1

9. Glycogen metabolism 2 1 1

10. Pentose phosphate pathway 1 1

11. Metabolism of Monosaccharides and Disaccharides 1 1 1

12. Fatty acid oxidation 1 1

13. Fatty acid synthesis 1 1 1

14. Lipogenesis 2 1 1

15. Ketone bodies metabolism 1 1 1

16. Lipolysis 1 1

Total 30 15 15


9

CLINICAL BIOCHEMISTRY DEPARTMENT STAFF LISTING

The following is a list of the faculty members and staff of the Department of Clinical

Biochemistry. Students are welcome to contact any of the members of the department to

answer any of their inquiries.

Male Section: Men Medical Complex

Name/Status Room

No Phone No E-Mail Address Office Hours

Dr. Zainy M. A. Banjar 2/945 51-048, 22-116 [email protected] Daily

B.Pharm., M.Sc., Ph.D. 2/948 22-101, 22-176 11.00-12.00

Associate Professor

Chairman

Prof. Adil Abdel Rafee 2/946 22-112, 22-194 [email protected] Daily

M.B., B.ch., D.M.Sc.,Ph.D. 2/924 22-102, 22-173 12.00-1.00

Professor

Prof. Mohammed Ali Ajabnoor 2/942 22-100, 22-174 [email protected] Sat, Mon, Wed

B.Pharm.,M.S., Ph.D.

1.00-2.00

Professor

Prof. Mohammed Saleh Ardawi 2/925 22-103, 22-177 [email protected]

B.Med. Sc., M.A., Ph.D.

Professor

Prof. Zohair M. H. Marzouki G/640 51-701 zmarzouki@ Kau .edu .sa Daily

B.Pharm., M.Sc., Ph.D. 2/853 22-099, 22-170

12.00-1.00

Professor

Dean Off., Faculty of

Pharmacy

Prof. Abdulwahab A. Noorwali 2/911 22-097, 22-172 [email protected]

B. Phar., Ph.D. Professor

Prof. Mohammed Zelai A. Abdu 2/852 22-098, 22-169 [email protected] Sat, Sun, Mon

B.Sc., M.Sc., Ph.D. 1.00-2.00 Associate Professor


10

Prof. Mamdouh Youssef Souaida 2/940 22-128

drmamdouhyoussef

@yahoo.com

Sat, Sun, Mon

M.B.ch., M.Sc.,Ph.D.

1.00-2.00

Associate Professor

Dr Osama Abdul Aziz 2/910 22-096 [email protected] Daily M.B., B.ch., M.D. 8.00-10.00

Associate Professor

Dr Mohammed A Hassanien 2/941 22-118

mohammedhassanien700

@hotmail.com

Daily

M.B., B.ch., M.D.

WWW.kaau.edu.

sa/mhassanien

8.00-10.00

Assistant Professor

Dr. Mohammed Shoaib Jarullah 2/912 22-130 [email protected]

B.Sc., M.Sc., Ph.D. Lab 22-120, 22-121

Technician

Mr. Khalil Fadul Al-Moula 2/914 22-129

B.Sc. Technician. Lab 22-120, 22-121

Mr. Ahmad Al-Shamrani 2/922 22-117 [email protected]

B.Sc. Lab 22-120, 22-121

Technician


11

Female Section: Women Medical Complex

Name/Status Room

No Phone No E-Mail Address Office Hours

Prof Suhad Matoug Bahijri 2/510 23-429 [email protected] B.Sc.,M.Sc., Ph.D. Professor

Prof Enayat Mohd. Hashem 2/513 23-441 [email protected] M.B., B.ch., h.D. Professor

Dr Amina Mohd. Al-Ghareeb 2/551 23-448 [email protected] M.B., B.ch., h.D. Associate Professor

Dr Huda Gad 2/550 23-447 [email protected] M.B., B.ch., h.D. Assistant Professor

Dr. Eman Mokbel Alissa(BSc

MSc PhD) Assistant Professor 23-432

[email protected]

Webpage:

www.kau.edu.sa/ealissa

Dr. Fayza F Al Fayez (BSc MSc PhD ) Assistant Professor

23-431 [email protected]

Ms. Areej Al-Turki 2/514 23-442 [email protected] B.Sc. Technician.

Zain Mohd.AL-Shareef 2/613 23-433 B.Sc. Technician.

Hana Abdullah Basaffar 2/620 23-436 B.Sc. Technician.

Rehab Aboobakar Al-Aydoos 2/618 23-437 [email protected] B.Sc. Technician.

Nada Saleh Al-Saykhan 2/618 23-437 [email protected] B.Sc. Technician.

Reem Foad Ghazali 2/622 23-601 [email protected] B.Sc. Technician.

Department Web Site

www.kau.edu.sa/faculties/medicine/dcbcweb


12

Icons The following icons have been used to help you identify the various experiences

you will be exposed to.

Learning objectives

Content of the lecture

Independent learning from textbooks

Independent learning from the CD-ROM.

Independent learning from the Internet

Home Work

Problem-Based Learning

Self- Assessment (the answer to self-assessment exercises will be

discussed in tutorial sessions)

The main concepts


13

Lectures


14

Lectures # (1-3) : Allosteric protein

DEPARTMENT: Clinical Biochemistry

Tutor: Dr.

TEACHING LOCATION: Auditorium

By the end of this lecture, you will be able to:

1. Relate the structural properties of particular proteins such as hemoglobin and myoglobin to their functions in human health and disease.

2. Discuss the genetic bases of protein structure and how molecular defects lead to diseases such as sickle cell anemia.

3. Be able to recognize the structure of the commonly found amino acids in specific proteins and explain the their importance.

• Hemoglobin:

• Quaternary structure of hemoglobin, cooperative binding of oxygen, effect of hydrogen ion and carbon dioxide (Bohr effect)

• Functional significance of DPG, fetal hemoglobin, abnormal hemoglobin, (sickle cell anemia).

• Myoglobin:

• Globular proteins, myoglobin configuration and conformation.

Student Notes:

.


15

• Oxygen binding site.

• Microenvironment and reversible oxygen binding.

Myoglobin and hemoglobin are two

oxygen – binding proteins with a very

similar primary structure. However,

myoglobin is a globular protein

composed of a single polypeptide chain

that has one O2 binding site. Hemoglobin

is a tetramer composed of two different

types of subunits. Each subunit has a

strong sequence homology to myoglobin

and contains an O2 binding site. A

comparison between myoglobin and

hemoglobin illustrates some of the

advantages of a multisubuniut

quaternary structure.

1. Required Texts And Resources: Lippincott

Illustrated Reviews, 3rd

edition, Champe &

Harvey P : 25 - 42

2. Reading Handouts will be distributed

3- Lectures and power point presentation

will be published on department website: www.kaau.edu.sa/faculties/medicine/dcbcweb

•

•

•

You have the opportunity to watch the CD-

ROM about Hemoglobin. You can access the

CD-ROM during your spare time.


16

1- Haemoglobin

http://www.ebi.ac.uk/interpro/potm/2005_10/Page1.h

2- Haemoglobin

http://www.iscid.org/encyclopedia/Haemoglobin

3- Haemoglobin animations

http://www.umass.edu/microbio/chime/hemoglob/2fr

t.htm

4- Oxygen dissociation curve

http://www.bio.davidson.edu/Courses/anphys/1999/D

s/Oxygendissociation.htm

5- Oxygen dissociation curve 2

http://www.ventworld.com/resources/oxydisso/dissoc

6- Haemoglobin dissociation curve 3

http://www.manbit.com/Hbdiss.htm

7- Carbon dioxide and Oxygen transport

http://cal.man.ac.uk/student_projects/2001/MNQC7N

omepage.htm

1- In a table form compare between

Hemoglobin and Myoglobin

including the difference in the :

Structure, Function, Oxygen binding

and Oxygen dissociation curve.

Clinical Question

A 67 – year old man presented to the

emergency department with one week history of

angina and shortness of breath. He complained

that his face and extremities had a "blue color" .

His medical history included chronic stable

angina trated with isosorbide dinitrate and

nitroglycerin. Blood obtained for analysis was

chocolate – colored. What is the possible

diagnosis


17

I- Short Questions:

a- What of the effects of the following on

oxygen dissociation curve of Hemoglobin

1- 2,3 – BPG

2- CO2

3- pH

b- What is the molecular defect which leads

to the following?

1- Sickle cell disease

2- Methemoglobinemia

3- Thalassemias

II- MCQ:

1- Hemoglobin is

A. A tetramer of 4 myoglobin proteins.

B. A tetramer of four globin chains and one

heme prosthetic group.

C. A dimer of subunits each with two distinct

protein chains (alpha and beta).

D. A dimer of subunits each with two

myoglobin proteins.

2- Hydrophobic amino acid sequences in

myoglobin are responsible for

A. Covalent bonding to the heme prosthetic

group

B. The folding of the polypeptide chain

C. The reversible binding of oxygen

D. b and c above

3- Cooperative binding of oxygen by

hemoglobin

A. Is induced by hemoglobin

B. Is a result of different affinities for oxygen

by each subunit protein

C. Is induced by oxygenation

D. Is a result of interaction with myoglobin


18

III- True / False

a. Proteins often consist of multiple

subunits so that they may have

different functions under different

conditions.

b. The porphyrin prosthetic group is

held into the interior of globin

molecules by covalent bonds to

specific amino acid residues

c. Myoglobin has a greater affinity

for oxygen than hemoglobin.

d. Cooperative binding and

allosterism of hemoglobin allow

oxygen to be unloaded at low

partial pressures of oxygen in the

tissues.

e. The Bohr effect is a description of

the effect of pH on hemoglobin,

oxygen bound more tightly at

f. low pH (in tissues) and less tightly

at higher pH values.


19

Lecture #(4) : Collagen

DEPARTMENT: Clinical Biochemistry

Tutor: Dr.

TEACHING LOCATION: Auditorium

By the end of this topic the student shall be able to:

1. Understand the role of the

extracellular matrix

2. Understand the components of

the extracellular matrix

3. Understand the structure and

synthesis of collagen fibers

• Collagen.

• Synthesis and post-translational

modification of collagens.

• Noncollagenous proteins in the

extracellular matrix.

Collagen is on of the components of the extracellular matrix (ECM), which present outside of the cell. This matrix, even from a basic list of its components; proteins, glycoproteins, glycosaminoglycans, and many other large and small biological molecules, can


20

been seen as complex. Furthermore there is no one specific ECM with great variation from tissue to tissue and also specific functional specializations. This lecture will attempt therefore to only cover a Collagen as a part of ECM.



edition, Champe &

Harvey P :




•

•

•


ROM about Collagen You can access the CD-

ROM during your spare time.

1-Extracellular matrix (Collagen)1

http://cellbiology.med.unsw.edu.au/units/science/l

e0508.htm

2 –Extracellular matrix (Collagen) 2

http://cellbiology.med.unsw.edu.au/units/pdf/anat

L8s4.pdf

3-Extracellular Matrix lecture

http://www.owlnet.rice.edu/~bioc341/notes/lec23.p

Do the proline side groups (rings) point inward (to the center of the axis of the triple helix), or do they point out? You can change the "display" to "backbone" then back to "sticks" to see where the side groups of proline are.


21

1- Explain how collagen structure

serves its function in different body

tissues

I- Short Questions:

1- How many amino acid chains are present in this model of collagen?

2- Of the 20 possible amino acids, how many are present in this model of collagen? 3- What is the repeating pattern of these amino acids?

II- MCQ: 1- Substitution of Gly in the primary

sequence of collagen with almost any other

amino acid results in defective collagen

assembly because:

A. collagen is glycosylated on Gly residues. B. Gly forms critical hydrogen bonds with

neighboring glycines. C. the contact points of the triple helix are

so close that only the Gly side chain fits well into the space available.

D. Gly is crosslinked to allysine residues in the mature protein.

2- The collagen defect present in scurvy is

A. substitution of gly for pro and lys residues in the collagen sequence.

B. decreased protein stability due to decreased hydroxylation of pro and lys residues.

C. conversion of the collagen helix from a right- to a left-handed triple supercoil.

D. decreased protein stability due to increased glycosylation.


22

III- True / False a- Ascorbic acid is necessary for the formation

of hydroxyproline and hydroxylysine

residues before they are incorporated into

the collagen protein molecule.

b- All collagen types have a triple helical

structure.

c- In Collagen molecules, Hydroxyproline

is formed by the posttranslational

hydroxylation of peptide-bound proline

residues catalyzed by the enzyme prolyl

transferase.


23

LECTURE # (5) : Introduction to the enzymes

DEPARTMENT: Clinical Biochemistry TUTOR: TEACHING LOCATION: Auditorium

By the end of this lecture you will be

able to:

1. Summarize the importance of

enzymes in many aspects in health

and disease

2. Describe general properties of

enzyme molecule and the process

of enzyme catalysis

3. Define terms used in enzymology

4. Compare and contrast between

enzymes and inorganic catalysts

5. Identify the nomenclature of

enzymes

6. Outline the classification of

enzymes

7. Distinguish the different types of

enzyme specificity

• Enzymes are important for medical students for diagnosis and treatment

• Enzymes are typically large globular proteins that accelerate reactions by million folds

Student Notes:

.


24

• Substrate, product, apoenzyme, holoenzyme, cofactor, coenzyme, active site and catalytic site, all are terms used in study of enzymes

• There are many differences between enzymes and inorganic catalysts as reversibility and specificity of enzyme action

• Naming of enzymes is either convenient for everyday use, or more complete systematic name divided into six major classes

• Enzyme specificity are absolute, relative, stereochemical and group

Remember that all reactions in the body are

mediated by enzymes, which are protein catalysts

that increase the rate of reactions without being

changed in the overall process. Enzymology is

important as inborn errors of metabolism are due

to deficiency of some enzymes. Also assay of

particular enzymes can help in diagnosis of many

diseases. The most striking characteristics of

enzymes are their catalytic power and specificity

which is of many types.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey , chapter 27 ( pp:365-367)

2. Supplementary Texts And Resources: Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby. Chapter 18 (pp:217-218)

•


25

•

• You have the opportunity to watch the CD-ROM about enzymes. You can access the CD-ROM during your spare time.

1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html

2- http://www.stolaf.edu/people/qiannini/fashanimat/enzymes

3- http:// www.reachoutmichigan.org/funexperiments/quick/eric/enzymes

4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid

5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd

6- http://www.wiley.com/legacy/college/boyer/0470003790

7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html

8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity.

** Enzymes are biological catalysts that

accelerate the rate of reaction, by using

the library and the internet try to explain

how this occurs.

Clinical Case: A 52-year-old-man

presented at ER of a hospital

with severe chest pain which had

present for the past hour. He had


26

a 2-year history of angina of

efforts. How can you use

enzymes in?:

a. Diagnosis of this case

b. Treatment of it

I- Short Questions:

1- Enumerate enzyme specificity

2- Differentiate between enzymes

and inorganic catalysts

II- MCQ: 1.Enzymes are:

a) Proteins

b) Chloroplasts

c) Genes

d) Mitochondria

2. Enzymes are catalysts. They increase the

rate of chemical reactions by:

a) Raising the activation energy

b) Temporarily increasing the temperature

c) Covalently binding the substrate

d) Lowering the activation energy

3. Enzymes are classified by the:

a) Size of the enzyme

b) Size of the substrate

c) Type of reaction

d) Rate of reaction

4. Shown below is a graph describing energy

versus reaction coordinate for a catalyzed

and uncatalyzed reaction. Fill in the blanks

with the letter that corresponds to each stage

of the graph.


27

_____ ES

_____ S (substrate)

_____ P (product)

_____ Uncatalyzed reaction

III- Complete the following:

Some enzymes require another chemical to

function. These helper compounds are called

__________. If a cofactor is covalently bound to the

enzyme, it is called a __________ group. An

enzyme with its cofactor attached is called a

__________, while an enzyme minus its extra

component is called an __________.


28

LECTURE # (6) : Mechanism of enzymatic catalysis



able to:

1. Describe the two models of binding

the enzyme to its substrate

2. Identify what is meant by transition

state

3. Understand the difference between ∆G and ∆G‡

4. Explain the mechanism of enzymatic

catalysis by acid-base catalysis,

covalent catalysis, substrate strain

and entropy effect

• Two models have been proposed to explain how an enzyme binds its substrate; lock-and-key model and induced-fit model

• Lock-and-key model assumes that an enzyme active site will accept a specific substrate

• Induced-fit model recognizes that there is much flexibility in an enzyme’s substrate . Accordingly, an enzyme is able to conform to a

Student Notes:

.


29

substrate

• Transition state is state of maximum energy through which the enzymatic reaction proceeds. It is not an intermediate compound.

• The differences in free energy (∆G) between the transition state and substrate is the free energy of activation (∆G‡)

• Enzyme can enhance the rate of reaction by four processes: general/acid base catalysis, covalent catalysis, substrate strain and entropy effect

When correctly positioned and bound on the

enzyme surface, the substrate may be “strained”

toward the transition state. At this point the

substrate has been “set up” for acid-base and/or

covalent catalysis. Proper and the nearness of the

substrate with respect to the catalytic groups

(proximity effect) contribute to decrease in

entropy and so enhance the rate of enzymatic

reaction.


2.Supplementary Texts And Resources: Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby. Chapter 18 (pp:217-218)

•

•



30

1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html

2- http://www.stolaf.edu/people/qiannini/fashanimat/enzymes 3- http:// www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid

5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6-http://www.wiley.com/legacy/college/boyer/0470003790

7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity 9- http://www.bio.winona.edu/berg/308/oldexam/308exam1.txt

** How does the enzyme bind its

substrate?

By using the library and the internet

try to answer this question.

I- Short Questions:

1. What is meant by transition

state


31

2. Enzymes can enhance the rate

of reaction. Enumerate the

processes by which this occurs.

II- MCQ: 1. The minimum amount of energy necessary

for a molecule(s) to react is the:

a) Activation energy

b) Free energy

c) Thermal energy

d) Potential energy

2. The state produced when two or more

molecules collide with just the right energy

and just the right orientation so that a

chemical reaction might occur is:

a) Catalytic state

b) Transition state

c) Activation state

d) Transient state

3. One of the following statement describing

the mechanism of enzyme action is

INCORRECT:

a) Many enzymes have flexible structures

that allow them to enfold their substrate

b) The substrate is often distorted when it

enters an enzyme-substrate complex

c) Amino acid side chains involved in the

formation of the active site center are

usually close together in the amino acid

sequence of the enzyme protein

d) Amino acid side chain near the active

site center often have a role in the catalytic

process

4.Which of the following statement about

enzyme catalyzed reaction is NOT TRUE:

a) Enzymes form complexes with their

substrate

b) Enzymes increase the activation energy

for chemical reaction

c) Many enzymes change shape slightly

when substrate binds

d) Reactions occur at the “active site” of

enzymes, where a precise quaternary

orientation of amino acids is an

important feature of catalysis


32

III- Complete the following: Enzymes carry out different chemical reactions in

catalysis. Fill in the blanks with the name of the

mechanism that matches with the example described

in each line. Mechanism names to choose from are:

covalent catalysis, acid-base catalysis, and metal ion

catalysis.

__________ catalysis may involve Glu, Asp, His, Lys,

or Arg residues.

__________ catalysis may involve Na+, K

+ or Mg

2+,

Ca2+

.

__________ catalysis may involve serine proteases.


33

LECTURE # (7) : Enzyme kinetics


By the end of this lecture you will be able

to:

1. Distinguish the several terms used in

enzyme kinetics as rate or velocity,

rate constant, order of a reaction,

turnover number ..etc

2. Identify Michaelis-Menten equation

and Linweaver-Burk equation

3. Recognize the factors affecting

enzyme activity as substrate

concentration, pH and temperature

• The enzyme (E) combines with its substrate (S) to form an enzyme-substrate complex (ES).

• The ES complex can dissociate again to form E + S, or can proceed chemically to form E and the product P.

• The rate constants k1, k2 and k3 describe the rates associated with each step of the catalytic process.

Student Notes:

.


34

• The initial velocity (Vo) at low substrate concentration is directly proportional to [S], while at high substrate concentration the velocity tends towards a maximum value (Vmax) which is independent of [S].

• Michaelis-Menten equation describes a “hyperbolic curve” of the relationship between [S] and velocity of the reaction

• Lineweaver-Burk plot (double reciprocal plot) gives a straight line if Vo is measured at different substrate concentration

• Not only substrate concentration , but also pH and temperature can affect enzymatic activity

• Kinetics is a study of the rate of changes of

substrates to products. Kinetics properties for many

enzymes reveals that, the rate of catalysis V varies

with [S] in a hyperbolic manner which is expressed in

Michaelis-Menten equation. Lineweaver-Burk plot

gives a straight line of relationship between [S] and

the rate of reaction..



•

•



35

1.http://web.indstate.edu/thcme/mwking/enzyme-kinetics 2.htmlhttp://www.stolaf.edu/people/qiannini/fashanimat/enzymes 3.http:// www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 4.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid 5.http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6.http://www.wiley.com/legacy/college/boyer/0470003790 7.http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8. http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity.


try to illustrate the relationship between

substrate concentration and reaction

velocity.

I- Short Questions:

a) Would you think that all enzyme

assays need the same pH? Why?

b) What is the meaning of optimum

temperature?

II- MCQ: 1. Which of the following does not influence

enzyme activity?

a) pH

b) Temperature

c) Product degradation

d) Substrate concentration


36

2. The Michaelis constant Km is:

a) Numerically equal to ½ Vmax

b) Dependent on the enzyme concentration

c) Independent on pH

d) Numerically equal to the substrate

concentration that gives half-maximal velocity

What effect does temperature have on enzymes?

a) Boiling will denature them, as will being too

cold

b) Boiling will not harm them, but being too

cold will denature them

c) Boiling and cooling will both reduce the

speed of their rate

d) Boiling will denature them, but cooling will

only slow down their work

4. The Michaelis-Menten equation is Vo=Vmax

[S]/(Km+[S]).

Fill in the blanks with the letters shown to correctly

label each part of the graph

_____ Vmax

_____ [S]

_____ Vo

_____ Point used to determine the Km

III- Complete the following: Often the kinetic values of an enzyme are

plotted using the Lineweaver-Burk

equation:

1/vo=Km/Vmax·1/[S] +1/Vmax

Enter "yes" or "no" to indicate if the

equation and graphical terms match in each

statement.

_____ Y-intercept and -1/Km

_____ X-intercept and 1/Vmax

_____ Slope and Km/Vmax


37

LECTURE # (8) : Enzyme inhibitors



able to:

1. Outline the importance of enzyme

inhibition studies

2. Discriminate the two broad classes of

enzyme inhibitors that based on the

extent of inhibition

3. Compare the mechanisms of enzyme

inhibition

4. Interpret the use of enzyme inhibition

as drugs in the treatment of diseases

• There are two broad classes of enzyme inhibitors: reversible and irreversible

• Reversible inhibitors interact with an enzyme via noncovalent association

• Irreversible inhibitors interact with an enzyme via covalent association

• Competitive inhibitors binds only to enzyme (E) and not to enzyme-substrate complex (ES)

• Noncompetitive inhibitors binds either to (E) and/or to (ES)

• Uncompetitive inhibitors binds only

Student Notes:

.


38

to (ES) and not to (E)

• Enzyme inhibition may affect Vmax or Km or both

• Many natural occurring and man-made compounds are irreversible enzyme inhibitors

• There are therapeutic application for enzyme inhibition

A competitive inhibitor prevents the substrate from

binding to its enzyme, while noncompetitive or

uncompetitive do not. Competitive inhibitor increases

Km without change Vmax. Noncompetitive inhibitor

decreases Vmax without change in Km. But

uncompetitive inhibitor decreases both Vmax and Km

.



•

•


1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html 2- http://www.stolaf.edu/people/qiannini/fa


39

shanimat/enzymes 3- http:// www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid 5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6- http://www.wiley.com/legacy/college/boyer/0470003790 7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity.

**How can the irreversible inhibitors

bind the active site of the enzyme?


try to explain how this occurs.

Clinical Case: A young girl was

brought to the pediatric clinic with

infected wound on her knee. The

mother was instructed to give the

child penicillin. The child had

improved after a week.

a) What the possible mechanism

of action of this antibiotic?

b) What is the target enzyme of

penicillin?

I- Short Questions:

1. Classify enzyme inhibitors

2. Tabulate the effect of competitive,


40

noncompetitive and

uncompetitive on Vmax and Km

II- MCQ: 1. Which type of reversible enzyme inhibitor

binds to the free enzyme and the enzyme-

substrate complex?

a) Noncompetititive

b) Competitive

c) Uncompetitive

d) None of the above

2. In competitive inhibition, one of the following

statement is CORRECT:

a) Vmax is increased

b) The concentration of active enzyme

molecule is unchanged

c) The apparent Km is increased

d) The apparent Km is decreased

3. Enzyme action can be influenced by the

presence of inhibitors. Which of the following

statements correctly matches the type of

inhibitor with its effect on an enzyme.

a) Irreversible and Renders the enzyme

permanently inactive

b) Competitive and Inhibitor binds only to

ES complex, only important when[S]

high, Vmax lower, Km lower

c) Noncompetitive and Can be overcome

with high [S], Vmax unchanged, Km higher

d) Uncompetitive and Cannot be overcome

with high[S], Vmax lower, but Km unchanged

4. In Lineweaver-Burk plot below:

a) Mention the type of inhibition of

enzymatic reaction

b) Which one of the lines of the plot

represents the enzymatic reaction

without inhibition?


41


Any molecule that acts directly on an

enzyme to lower its catalytic rate is

called ---------. Enzyme inhibition may

be of --------types. Reversible

inhibition can be overcome by-----but

this is not possible for -----------

inhibition.


42

LECTURE # (9) : Enzyme regulation



able to

1. Integrate enzymes into metabolic

pathways

2. Identify the terms of the rate-limiting

enzyme and the committed step in a

metabolic pathway

3. Know the different ways of enzyme

regulation under physiological and

pathological conditions

4. Recognize the allosteric regulation

5. Explain a feedback control

mechanism

• There are key enzymes in a metabolic pathway which can be regulated and hence control the pathway

• The activity of these enzymes can be regulated by:

• Changing the amount of enzyme by enzyme induction, enzyme repression, and enzyme degradation

• Changing the activity of enzyme by allosteric regulation, feedback control,

Student Notes:

.


43

covalent modification, and activation by cleavage

• Compartmentation of pathways is also a way of enzyme regulation

Control of a pathway occurs through modulation

of the activity of one or more key enzymes in the

pathway . The rate-limiting enzyme and the

committed step enzyme can be regulated by

changing the amount (enzyme induction, repression,

or degradation), or changing the activity (allosteric

regulation, feedback inhibition, covalent

modification, or enzyme cleavage) or

compartmentation of the pathways.



•

•


1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html 2- http://www.stolaf.edu/people/qiannini/fashanimat/enzymes 3- http:// www.reachoutmichigan.org/funexperime


44

nts/quick/eric/enzymes 4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid 5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6- http://www.wiley.com/legacy/college/boyer/0470003790 7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity. 9- en.wikipedia.org/wik/Enzymes 10.www.elmhurst.edu/~chm/vchembook/573 regulate

** By using the library and the internet

try to illustrate covalent modification of

an enzyme (e.g. glycogen phosphorylase)

II- Short Questions:

1. List some of the molecular

mechanisms by which the

catalytic activity of enzymes is

controlled.

2. Using a graph, illustrate the

kinetic behavior of an allosteric

enzyme

II- MCQ: 1. Allosteric enzymes are large, oligomeric

proteins that have catalytic sites for binding

substrates and regulatory sites that bind

effectors. The separate oligomers influence

one another; they work cooperatively. This is

evidenced by the characteristic rate curves

for allosteric enzymes which have:

a) Michaelis-Menten kinetics

b) Hyperbolic kinetics

c) Sigmoidal kinetics


45

d) Regulatory kinetics

2. Some enzymes are first synthesized in an

inactive form. These zymogens must undergo

proteolytic cleavage to produce the active

enzyme. Which of the following statements

are true of proteolytic cleavage?

a) It is reversible

b) It is irreversible

c) It is random

d) It occurs in the region of zymogen

synthesis

3. Increased synthesis of an enzyme is known

as:

a) Activation

b) Inhibition

c) Induction

d) Repression

4. In the graph below

a) Which one of the plot explains the

behavior of an allosteric enzyme?

b) What is the meaning of cooperativity?


The rate- limiting enzyme in a pathway is the

enzyme with the-------Vmax, while the enzyme

catalyzing the committed step is -----------.


46

LECTURE # (10) : Coenzymes and cofactors



able to:

1. Recognize the importance of

cofactors and coenzymes for the

enzymes

2. Identify vitamin-derived coenzymes

3. Distinguish some coenzymes that are

synthesized from common

metabolites

4. Relate classes and groups of enzymes

to some coenzymes

• Cofactors are required by

inactive apoenzymes to convert them into active holoenzymes

• Cofactors may be metal ions or organic compounds (coenzymes)

• Coenzymes may be freely dissociate from the enzyme, or may remain bound to its apoenzyme

• Metabolite coenzyme are S-adenosyl methionine, UDP-

Student Notes:

.


47

glucose

• Vitamin-derived coenzymes are NAD, NADP, FAD, FMN, TPP, PLP, CoA

• Some coenzymes are derived from fat-soluble vitamin as vitamin K

Biological oxidation-reduction reactions need

certain hydrogen carriers as NAD, NADP, and FAD.

Some transaminases need PLP, transacylases need

CoA , transmethylases require SAM, and

transketolases need TPP.

Biotin is required for certain carboxylases, while THF

is needed for transfer of one carbon moiety. Vitamin K

is needed for carboxylation of glutamate residue in

prothrombin.



•

•



48

1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html 2- http://www.stolaf.edu/people/qiannini/fashanimat/enzymes 3- http:// www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid 5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6- http://www.wiley.com/legacy/college/boyer/0470003790 7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity.

** By using the library and the internet

try to illustrate the active part in each of

the following coenzymes: NAD, FAD,

TPP, CoA, PLP and THF

Clinical Case:

A 37-year-old man had

developed enlarged liver that

was tender to palpation. AST

in serum and total plasma

bilirubin were found to be

elevated. A diagnosis of


49

hepatitis was made.

a) What is the coenzyme

needed for AST?

b) Mention two other

enzymes that need this

coenzyme.

I- Short Questions:

1. Mention the coenzyme needed for

each of the following:

carboxylases, transaminases,

transmethylases, and transacyalses

2. Give examples of some metal ions

that are cofactors and mention the

enzyme of each.

II- MCQ: 1. Many enzymes require cofactors to function.

Many of these cofactors are vitamins.

Which of the following statements is NOT

TRUE?

a) Fe, Zn, Cu, Mg, Mn, K, and Mo are

classified as vitamins

b) Humans have lost the ability to

synthesize vitamins

c) Vitamins are modified by the body to

form coenzymes

d) There are two classes of vitamins:

water-soluble and fat-soluble

2. From which of the following vitamins, a

coenzyme of transketolases is derived ?:

a) Vitamin B1

b) Vitamin B2

c) Vitamin B6

d) Vitamin B12

3. A coenzyme derived from Niacin is:

a) FAD

b) NAD

c) CoASH

d) PLP

4. Shown below is a coenzyme acts as a


50

hydrogen carrier

a) Give the full name of it

b) What is the name of the vitamin that is

derived from?

c) How can this coenzyme carry hydrogen

atoms?

III- Complete the following: Some enzymes require another chemical to

function. These helper compounds are called

cofactors. Cofactors may be_____, or__________.

Examples of vitamin-derived coenzymes

are:_____,________, and________. Metabolite-

derived coenzymes include________and_________


51

LECTURE # (11) : Enzymes in clinical practice



able to:

1. Evaluate the use of enzymes and

isoenzymes in the diagnosis of

diseases

2. Know the use of enzymes in

treatment of some diseases

3. Recognize the ribozymes and

catalytic antibodies

4. Identify the site-directed mutagenesis

• Enzymes are used clinically in three principal ways:

- in diagnosis and prognosis of various disease

- as analytical reagents in the measurement of activity of other enzyme or non-enzyme substances

- as therapeutic agents

• RNA enzymes (hammerhead ribozymes) and catalytic antibodies are recently discovered

• Site-directed mutagenesis is used for design a new drug therapy

Student Notes:

.


52

Isoenzymes are forms of an enzyme which are

structurally different but have similar catalytic

properties. Measurements of the isoenzymes of lactate

dehydrogenase (LDH), alkaline phosphatase (ALP),

and creatine kinase (CK) are of clinical value. Studies

have shown that catalysis for biochemical reactions

are not limited to naturally occurring proteins. Site-

directed mutagenesis (modification of amino acid

sequence of known enzymes) is used for design new

drug therapy.



•

•


1- http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html 2- http://www.stolaf.edu/people/qiannini/fashanimat/enzymes 3- http://


53

www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 4- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid 5- http://www.ncbi.nlm.nih.ov/entrez/query/fcgi?cmd 6- http://www.wiley.com/legacy/college/boyer/0470003790 7- http:/www.siu.edu/departments/biochem/som_pbl/ms_ppt_anim.html 8- http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20activity. 9- www.dcnutrition.com/Miscellaneous/Detail

**It was believed that all enzymes were

proteins till a recent discovery , by using

the library and the internet try to explain

this statement.

Clinical Case: A 52-year-old-man

presented at ER of a hospital with

severe chest pain which had

present for the past hour. He had a

2-year history of angina of efforts.

a) What specific tests would you

request from the biochemistry

laboratory?

b) How can use of an enzyme

share in the treatment of this

condition?

I- Short Questions:


54

1. Enumerate five enzymes used in

clinical diagnosis and mention

the major diagnostic use for

each

2. What are the causes of presence

of non-plasma specific

enzymes?

II- MCQ: 1. In normal blood, the alkaline phosphatase activ

mainly from:

a) Bone and small intestine

b) Bone and liver

c) Small intestine and placenta

d) Bone and placenta

2. How many different isoenzymes of normal

LDH can be identified by electrophoresis at pH 8.6

a) Two

b) Three

c) Four

d) Five

3. LDH assays are useful in diagnosing diseases

of the:

a) Heart

b) Pancreas

c) Liver

d) a and c


55

Lectures # ( 12 ) : Membrane Structure


By the end of this topic the you will be able to:

1. Comprehend the fluid mosaic model of biologic membrane.

2. Understand how change in membrane composition changes its function.

Chemical compositions of membranes:

• Separation of cells and intracellular organells into different chemical compartments by membranes.

• Lipids of membranes.

• Distribution of membrane lipids.

• Membrane proteins.

• Carbohydrates of membranes.

Molecular structure of membranes:

• The fluid mosaic model of biologic membranes.

• Asymmetry of membrane.Membrane fluidity


56

Membranes are highly viscous, plastic

structures. Plasma membranes form

closed compartments around cellular

protoplasm to separate one cell from

another and thus permit cellular

individuality. The plasma membrane has

selective permeabilities and acts as a

barrier, thereby maintaining differences

in composition between the inside and

outside of the cell.



edition, Champe &

Harvey P :




•

•

•


ROM about Membrane structure. You can

access the CD-ROM during your spare time.

1- Membrane structure

http://cellbio.utmb.edu/cellbio/membrane.htm

2- Biological membrane structure

http://www.pnas.org/cgi/content/abstract/66/3/615

3- Biological membrane structure


4- Membrane Composition



57

1- Draw a figure for cell membrane,

mention the basic composition for the

membrane and explain how membrane

structure serves its function?

I- Short Questions:

a- Which component (s) of membranes give

it its fluid characteristics?

b- Which part of a membrane helps it keep

its shape (prevents deformation)?

c- How are proteins arranged in a

membrane? What is the difference between

a transmembrane protein and a peripheral

membrane protein?

d- What feature in a membrane helps to

prevent freezing? Be specific.

II- MCQ: 1- Triacylglycerols cannot form lipid bilayers

because they A. Have hydrophobic tails

B. Do not have polar heads

C. Cannot associate with cholesterol

D. Have polar heads

2- In a typical eukaryotic plasma membrane

A. Proteins can move in and out of the bilayer

B. Lipids can move and diffuse through the bilayer

C. Some lipids can rotate within the bilayer

D. All of the above

3- The arrangement of lipid bilayers and other

components is the basis for the currently

widely accepted description which is called the

A. Lipid bilayer model B. Mosaic model C. Diffusion model D. Fluid mosaic model

III- True / False


58

A. According to the current model of cell

membrane structure, the two layers of

lipids in the bilayer are nearly identical

B. Cholesterol accounts for 20% to 25% of

the mass of lipids in a typical

mammalian plasma membrane

C. The distribution of peripheral

membrane proteins is generally identical

on both sides of a given membrane.


59

Lectures #(13) : Membrane Transport


By the end of this topic you will be able to:

1. Explain how molecules move through membranes and the forms of energy needed to derive this process and to differentiate between active and passive transport.

2. Appreciate the functional role of membrane proteins as pumps, gates,

channels and receptors.

Movement of molecules across membranes:

• Diffusion across cellular

membranes.

• Mediated transport passive

mediated transport system, active

mediated transport system: Na+

K+.

• ATpase, Ca2+ translocation and

Na+ dependent transport system.

• Endocytosis and phagocytosis

Student Notes:

.


60

Molecules can passively traverse the

lipid bilayer of the membranes down

electrochemical gradients by simple

diffusion or by facilitated diffusion. This

spontaneous movement toward

equilibrium contrasts with active

transport, which requires energy because

it constitutes movement against an

electrochemical gradient.



edition, Champe &

Harvey P :




•

•

•


ROM about Membrane transport. You can


1-Membrane transport 1

http://www.emc.maricopa.edu/faculty/farabee/bio

ioBooktransp.html

2-Transport across cell membrane

http://users.rcn.com/jkimball.ma.ultranet/Biology

s/D/Diffusion.html

3-Membrane transport mechanisms

http://physioweb.med.uvm.edu/bodyfluids/membr

htm

4- Cell membrane and transport mechanisms

http://staff.jccc.net/PDECELL/cells/transport.htm


61

1- In a table form, describe Major

mechanisms used to transfer material,

mention the characteristics of each of

them including the factor affecting and

the need for energy.

I- Short Questions:

1- Give the definition for the following:

a- Simple diffusion

b- Facilitated diffusion

c- Uniport, antiport, symport

d- Active transport

e- Endocytosis

II- MCQ: 1- Very large molecules (macromolecules)

can be transported across membranes by :

E. pores or channels with very large openings through the center

F. active transport proteins G. diffusion down a concentration gradient H. endocytosis or exocytosis

2- Another name for facilitated diffusion is

E. Active transport F. Transverse diffusion G. Lateral diffusion H. Passive transport

3- Facilitated diffusion (passive transport)

through a biological membrane is:

A. generally irreversible B. driven by the ATP to ADP conversion C. driven by a concentration gradient D. endergonic


62

III- True / False a- Proteins that transport water across cell

membranes are called aquaporins.

b- Symport and antiport proteins must be

active transport proteins.

c- Active transport involves the conversion of

ADP to ATP.

d- Endocytosis is the process by which cells

take up large molecules

e- In adipocytes and muscle, glucose enters by

facilitated diffusion


63

Lectures #(14) : Cellular transduction


By the end of this topic you will be able to:

1. The molecular mechanisms for regulation and action of protein kinases, protein phosphatases and G-proteins including small G- proteins of the Ras-superfamily and heterotrimeric G-proteins;

2. The molecular basis for signalling by reversible protein phosphorylation;

3. The molecular basis for targeting in signal transduction.

• Kinases & phosphatases

• Protein Kinase A (cAMP-

dependent protein kinase)

• G-protein signal cascade

• Structure of G-proteins

• Small GTP-binding proteins,

GAPs & GEFs

• Phosphatidylinositol signal

cascades

• Signal protein complexes


64

Cellular transduction is any process

by which a cell converts one kind

of signal or stimulus into another.

Processes referred to as signal

transduction often involve a

sequence of biochemical reactions

inside the cell, which are carried

out by enzymes and linked through

second messengers. Such processes

take place in as little time as a

millisecond or as long as a few

seconds.



edition, Champe &

Harvey P :




•

•

•


ROM about Cellular transduction. You can


1-Signal transduction power point presentation

www.smd.qmul.ac.uk/morbidanatomy/Cancerbiolo

gy/Cancer-Signal-transduction.ppt

2-Signal transduction lecture powerpoint 2

www.nida.nih.gov/whatsnew/meetings/frontiers/po

werpoint/howlett.ppt

3-Signal transduction lecture powerpoint 3


65

www.bmb.psu.edu/courses/bmmb598e/signaltrans.

pdf -

4- Signal transduction in tumor cells

www.mdc-berlin.de/signaltransduction

1- Diagram and describe the sequence of

events by which a hormone such as

epinephrine or glucagon activates

production of cyclic AMP within a cell.

Include the roles of the receptor (GPCR),

the different subunits of the stimulatory G

protein, and Adenylate Cyclase. How is the

signal turned off at each step? You may be

asked to briefly describe the role of one of

the following: AKAP, RGS protein.

2- Describe the activation of cAMP-

Dependent Protein Kinase. What causes the

enzyme to be inhibited in the absence of

cyclic AMP? How is activation by cyclic

AMP turned off?

Signaling pathways are a balance of positive

and negative signals. Cholera toxin, the

active agent of Cholera vibrio, causes an

increase in protein kinase A activity. From

this point of view, Explain how cholera

toxins produces its toxic effects?

I- Short Questions:

1- Diagram an example of the reaction

catalyzed by the activated cAMP-

Dependent Protein Kinase. What reaction is

catalyzed by the enzyme Protein

Phosphatase.


66

2- Write out (in words) the reaction

catalyzed by Phospholipase C. Describe the

"second messenger" roles of the two

products of the Phospholipase C reaction.

II- MCQ: 1- In signal transduction what is an effector

enzyme? A. An integral membrane protein that changes conformation upon binding of a ligand to a cell surface receptor. B.A small molecule that diffuses within a cell and carries a signal to its ultimate destination. C.A protein bound on the interior of a cell membrane that generates a second messenger. D.Protein bound on the exterior surface of a cell and is the receptor site for a ligand.

2- Which does not generally use a signal

transduction mechanism?

A.hydrophilic hormones B.neurotransmitters C.growth factors D.steroids

3- Which of the following enzymes is

involved in the activation of the protein

kinase C signaling pathway?

A- Ca2+

-ATPase

B.Gβγ C.phospholipase C D. DAG kinase

III- True / False

a- G proteins are are multisubunit proteins

consisting of , and subunits

b- In the adenyl cyclase signaling pathway the

second messenger is AMP

c- The toxins from cholera and whooping

cough both interfere with the proper

functioning of ATP synthesis.


67

LECTURE # (15- 16 ): Introduction to Metabolism, Bioenergetics, and the

Role of ATP


By the end of this lecture, you will be able to:

1. Compare and contrast catabolism and anabolism

2. Outline the general mechanisms for regulating metabolic pathways through enzymes.

3. Understand the role of ADP/ATP in connecting catabolic and anabolic reactions. How does the structure of these molecules allow them to mediate energy requiring reactions?

4. Compare the two physiological mechanisms for the net synthesis of ATP

5. Be able to determine the direction in which electrons would pass in an oxidation-reduction couple, given either ΔG’ or ΔE’.

6. Be familiar with the relative oxidation reduction potentials of NAD, FAD (FMN), ubiquinone, cytochromes c and a, and oxygen.

7. Understand the importance of various mitochondrial compartments in cellular energy production.

8. Explain the relationship between

Student Notes: .


68

electron flow and ATP production in the mitochondria (chemiosmotic theory of Peter Mitchell).

9. Describe the components of the electron transport chain, including the points where common inhibitors act.

10. Discuss the mechanism of ATP production in the mitochondria.

11. Understand the concepts of respiratory control and coupling.

• Metabolic Pathways

1- Definition, classification (Anabolism & Catabolism)

2- Catabolic phase 3- Low and high energy

bonds – ATP – ADP cycle

4- Mechanism of collection of energy

• Regulation of Metabolism 1- Signals from within the

cells 2- Communication

between cells 3- Intracellular messenger

systems

• Electron transport chain (ETC) 1- Components of ETC 2- Electron transport 3- Chemiosmotic

hypothesis 4- ATP synthesis 5- Inhibition of ETC 6- Uncouplers


69

In order to survive, humans must meet two basic metabolic requirements: we must be able to synthesize everything our cells need that is not supplied by our diet, and we must be able to protect our internal environment. In order to meet these requirements, we metabolize our dietary components through four basic types of pathways: Fuel oxidative pathways, fuel storage and mobalization pathways, biosynthetic pathways, and detoxification or waste disposal pathways.

1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 69 – 82 & P: 89 - 94


3- Lectures and power point presentation will be published on department website:

www.kaau.edu.sa/faculties/medicine/dcbcweb

•

•

• You have the opportunity to watch the CD-ROM about Bioenergetics and introduction to metabolism . You can access the CD-ROM during your spare time.

1- Overview of metabolism http://www.elmhurst.edu/~chm/vchembook/5900verviewmet.html

2- Introduction to metabolism (PowerPoint) http://www.rit.edu/~pac8612/Biochemistry/503(703)/ppt/Intr


70

oduction_to_Metabolism.ppt

3- Electro Transport chain(ECT) http://www.dentistry.leeds.ac.uk/biochem/lecture/etran/etran.htm

4- Electro Transport chain(ECT) http://vcell.ndsu.nodak.edu/animations/etc/movie.htm

5- ECT Animation

http://www.sp.uconn.edu/~terry/images/anim/ETS_slo

w.html

6- ATP Synthesis Animation

http://www.sp.uconn.edu/~terry/images/anim/ATPmit

o.html

7- ECT Movie

http://vcell.ndsu.nodak.edu/animations/etc/movie.htm

1- Regulation of metabolism is

based on need, from your studying

outline the factors regulating

metabolism and how they work

according to body needs?

2- Summarize the composition of

each of the respiratory chain

complexes I, III, and IV. Diagram the

pathway of electron transfer in the

mitochondrial inner membrane from

matrix NADH to oxygen, including

the smaller electron carriers,

coenzyme Q and cytochrome?

1- If sodium ions rather than

protons were pumped across

the mitochondrial membrane,

would there be any energy

available to couple to ATP

synthesis?

2- Clinical Question

The desire for a quick weight-

loss drug has led to a number

of disasters. In the 1930s,

dinitrophenol was explored as

a possible weight-loss aid, but

it had a variety of severe side

effects, including


71

hyperthermia and death. Why

was dinitrophenol a bad idea?

Explain how dinitrophenol

induces hyperthermia

I- Short Questions:

1- Give the definition for the

following:

a- Anabolic reaction

b- Catabolic reaction

c- Free Energy Change

d- Electron Transport Chain

2. Enumerate components of Electron

Transport Chain, How many ATP

molecules will be produced from

oxidation of One NADH+H+,

FADH2 respectively, in the chain?

3- How cAMP activates some

metabolic reactions and inhibits

others?

II- MCQ:

1. In the mitochondria NADH and QH2 are

oxidized by ____________.

(a) carbon dioxide

(b) hydrogen peroxide

(c) ozone

(d) oxygen

2. The synthesis of one molecule of ATP

from ADP requires _________ to be

translocated across the inner mitochondrial

membrane.

(a) one proton

(b) about two protons

(c) hundreds of protons

(d) 1 mole of protons


72

3. The degradation of which class of

biochemicals does not significantly

contribute to the release of

energy to cells?

(a) nucleic acids

(b) Proteins

(c) Lipids

(d) carbohydrates

III- True / False a. The biochemical reactions that

degrade molecules, such as

nutrients, are called anabolic

reactions

b. Metabolic pathways generally

have easily distinguished

starting and stopping points

c. All metabolic reactions occur in

the cytosol of cells

d. In mammals the enzyme

complexes of oxidative

phosphorylation are in the inner

mitochondrial

e. Most of the free energy needed

to drive ATP formation in the

mitochondria is the result of an

electrical contribution from a

charge gradient across the

inner mitochondrial membrane

matrix.


73

LECTURE # (17- 18) : Glycolysis


By the end of this lecture you will

be able to:

1- Define glycolysis, form a working

definition knowing the substrates

and products involved and any

other key intermediates produced.

2- Trace tissue location of

glycolysis, particularly tissues or

cells in the body where the

pathway is most important.

3- Locate the cell site of glycolysis,

where in the cell it occurs

(cytosol).

4- Describe the sequence of events,

the overall reaction sequence and

the number of stages and

reactions:

a. Material Flow:: Trace the

fate of labeled carbon or

other elements through the

pathway

b. Energy flow: Trace the

production and consumption

of ATP

Student Notes:

.


74

c. Electron flow: trace the


of reducing power

5- Identify the Key steps, either

those which form major control

sites or those which are main "

branch points"

6- Describe connections to other

pathways especially citric acid

cycle .

• Overview of Glycolysis

• Coupled Reactions in Glycolysis

• First Phase of Glycolysis

• Second Phase of Glycolysis

• Metabolic Fates of NADH and Pyruvate

• Anaerobic Pathways for Pyruvate

• Energetic Elegance of Glycolysis • Other Substrates in Glycolysis

The glycolytic pathway is employed by all tissues for the breakdown of glucose to provide energy ( in the form of ATP) and intermediates for other metabolic pathways.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey

2. Supplementary Texts And Resources: Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby


75

•

•

• You have the opportunity to watch the CD-ROM about glycolysis. You can access the CD-ROM during your spare time.

1. Introduction to Glycolysis:

http://www.terravivida.com/vivida/glyin2. Glycolysis Lecture:

http://web.indstate.edu/thcme/mwkingolysis.html

3. Glycolysis Animation: http://www.johnkyrk.com/glycolysis.ht

4. Glycolysis Home: http://biotech.icmb.utexas.edu/glycolysis/glycohome.html

3- List the enzymes that convert glucose

to glyceraldehyde 3-PO4. Add to your

list the substrates, products, and

cofactors for each of these enzymes. It

might be handy to make up a table

for this.

4- List the enzymes that convert

glyceraldehyde 3-PO4 to pyruvate.

Add to your list the substrates,

products, and cofactors for each of

these enzymes. It might be handy to

make up another table for this.


Predict the effect of a GLUT4

knockout (in mice) on the levels


76

of blood glucose before and after

a meal. Search the Internet and

report whether your predictions

were confirmed by experiment.

Of what use is a GLUT4 knockout

mouse?

3- Clinical Case

Ahmed entered the stadium

for the final lap of his

marathon race. He was well

ahead of his competitors. In

the last few minutes, he

became confused. In the

stadium, he started running

around the track in the wrong

direction and then collapsed.

What went wrong?

I- Short Questions:

1- Give the cellular location of the

glycolytic pathway.

2- Where is NADH produced ?

3. Which step produces ATP? Which

one of these is considered to be

'substrate level phosphorylation?

4- Name the enzyme that makes

anaerobic glycolysis possible by

using up the NADH that

accumulates.

5 -Consider the ten steps of glycolysis,

starting with glucose. What would

be the effect on pyruvate

concentration (increase, decrease

or none) of increasing the

concentration of the following?

Give a brief (one sentence)

explanation for your answer.

a) ATP


77

b) AMP

c) citrate

d) fructose-1,6-bisphosphate

e) fructose-2,6-bisphosphate

II- MCQ:

1- Which of the following

metabolites does not regulate

glycolysis in liver cells?

A. glucose-6-phosphate

B. fructose-6-phosphate

C. fructose-1-phosphate

D. fructose-2,6-bisphosphate

2-During kinase reactions, the role

of magnesium ions is to

A. be catalytic metals at the active sites

of the enzymes.

B. interact with the hydroxyl groups of

the various sugar molecules.

C. interact with the negative charges on

phosphate groups.

D. provide a bridging atom between

substrate and product, stabilizing

the transition state.

3- Which of the following is not a

substrate for hexokinase?

A. glucose

B. fructose

C. galactose

D. mannose

3- How many ATP molecules are

produced from glucose during

anaerobic glycolysis?

A. 0

B. 1

C. 2


78

D. 3

III- True / False a. Four molecules of ATP are

consumed per glucose

during the hexose stage

of glycolysis

b. The reaction catalyzed by

PFK-1 is metabolically

reversible

c. Mammals can convert

pyruvate to either ethanol

or lactate depending on

the availability of oxygen

d. Glucose is normally

transported into cells by

an active transport

protein since the

concentration of glucose

inside cells is normally

higher than that in the

blood.

e. Two molecules of ATP are

consumed per glucose

molecule during the

hexose stage of glycolysis


79

LECTURE # (19) : Tricarboxylic Acid Cycle (TCA)



be able to:

1. Define TCA, form a working




2. Trace tissue location of TCA,

particularly tissues or cells in the

body where the pathway is most

important.

3. Locate the cell site of TCA, where

in the cell it occurs (Mitochondria).

4. Describe the sequence of events,


the number of stages and reactions:

a- Material Flow:: Trace the fate of

labeled carbon or other elements

through the pathway

b- Energy flow: Trace the production

and consumption of ATP

c- Electron flow: trace the production

and consumption of reducing

power

5. Identify the Key steps, either those

which form major control sites or

those which are main " branch

points"

Student Notes:

.


80

6. Describe connections to other

pathways related to carbohydrate,

lipid and amino acids metabolism

7. Describe the amphibolic aspects of

TCA and the role of its

intermediate in various metabolic

process.

8. Diagram the shuttles for the transport of cytoplasmic reducing equivalents into the mitochondria

• Overview of TCA

• Reaction of the TCA cycle a- Oxidative decarboxylation

of pyruvate b- The eight sequential

reactions of TCA

• Energy produced by the cycle

• Regulation of the TCA cycle

The tricarboxylic acid cycle (TCA) is also called citric acid cycle or Kreb's cycle. It is the major final common pathway of oxidation of carbohydrates, lipids and proteins since their oxidations yield Acetyl Co A. It also plays a major role in lipogenesis,gluconeogenesis, transamination and deamination.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 107 – 114


81

2. Supplementary Texts And Resources:

Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby

You have the opportunity to watch the CD-ROM about TCA. You can access the CD-ROM during your spare time.

1- TCA animation http://www.science.smith.edu/departments/Biol

Bio231/krebs.html 2-TCA animation http://www.wiley.com/legacy/college/boyer/0470

90/animations/tca/tca.htm 3- TCA http://www.sigmaaldrich.com/Area_of_Interest/L

Science/Metabolomics/Key_Resources/Meta_Pathways/TCA_Cycle.html

4- Step by step Kreb’s cycle http://www.terravivida.com/vivida/tcasteps/ 5- Biochemistry animations http://www.wiley.com/college/fob/anim/

a. Diagram the Krebs Citric Acid Cycle,

beginning with pyruvate, giving the

names of all enzyme substrates and

products and names of enzymes (no

abbreviations). Indicate where NAD+,

NADH, FAD, FADH2, GDP, Pi, GTP,

coenzyme A, H2O, or CO2 are

substrates or products of reactions.


82

b. What is the fate of reducing equivalents

of FADH2 generated in Krebs Cycle?


A patient diagnosed with

thiamine deficiency exhibited

fatigue and muscle cramps.

The muscle cramps have been

related to an accumulation of

metabolic acid. What is the

metabolic product leads to this

condition? Explain your

answer.

I- Short Questions:

1- What is the intercellular location of

TCA?

2- What is the sources of Acetyl

CoA?

3- What are the products of TCA?

4- Describe the functions of 2

intermediates of TCA?

5- Summarize the functions of TCA.

II- MCQ:

1- The citric acid cycle oxidizes

pyruvate and some of the pathway

intermediates are starting

materials for many biosynthetic

pathways. This means the citric

acid cycle is a/an

______________. A. amplifying pathway

B. strictly catabolic pathway

C. anaerobic pathway

D. amphibolic pathway


83

2- In eukaryotes the enzymes of

the citric acid cycle are found in the

_________. A. cytosol

B. mitochondria

C. nucleus

D. endoplasmic reticulum

3- The enzyme pyruvate

translocase is located

______________. A. in the cytosol

B.in the inner mitochondrial

membrane

C. in the mitochondrial matrix

D. in the endoplasmic reticulum

III- True / False 1- The overall goal of the citric

acid cycle is to oxidize

pyruvate, form reduced

coenzymes and produce ATP

2- The citric acid cycle is an

anaerobic pathway that occurs

in the mitochondria of

eukaryotes.

3- ATP is consumed by the

pyruvate dehydrogenase

complex during the synthesis

of acetyl CoA

4- The citric acid cycle can be

viewed as a multi-step catalyst

simply because it returns to its

original state after each round

of reactions.

5- Isocitrate is more easily

oxidized than citrate because

it has a secondary alcohol

group, whereas citrate's

alcohol group is tertiary


84

LECTURE # (20) : Gluconeogenesis

D DEPARTMENT: Clinical Biochemistry TUTOR: TEACHING LOCATION: Auditorium


able to:

1- Define Gluconeogenesis, form a

working definition knowing the

substrates and products involved

and any other key intermediates

produced.


gluconeogenesis, particularly

tissues or cells in the body where

the pathway is most important.

3- Locate the cell site of

gluconeogenesis, where in the cell

it occurs (cytosol) Except for the

carboxylation of pyruvate, which

occurs in mitochondria.




a. Material Flow:: Trace the fate of

labeled carbon or other elements

through the pathway

b. Energy flow: Trace the production

and consumption of ATP

c. Electron flow: trace the production

and consumption of reducing

Student Notes:

.


85

power



the number of stages and reactions

6- Identify the Key steps, either those

which form major control sites or

those which are main " branch

points"


pathways, especially glycolysis and

the reciprocal regulation of both

pathway

8- Identify the non carbohydrate

sources of gluconeogenesis.

• Overview of gluconeogenesis

• Substrates for gluconeogenesis

• Reactions unique to gluconeogenesis

• Regulation of gluconeogenesis

Gluconeogenesis is ' production of glucose from non – carbohydrate sources' For a period of starvation of longer than about 12 hours. This pathway is very important for tissues which require a continuous supply of glucose as a metabolic fuel such as the brain, red blood cells, kidney medulla, lens and cornea of the eye, testes and exercising muscle.


86

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey p: 115 - 122


•

•

• You have the opportunity to watch the CD-ROM about gluconeogenessis. You can access the CD-ROM during your spare time.

1- Gluconeogenesis

http://web.indstate.edu/thcme/mwking/gluconeogenesi

s.html

2- Gluconeogenesis

http://www.answers.com/topic/gluconeogenesis

3- Gluconeogenesis animation

http://www.wiley.com/college/fob/quiz/quiz15/15-

22.html

4- Gluconeogenesis powerpoint presentation

http://www.sb.fsu.edu/~chapman/Classes/Bch4054/Co

ntent/Gluconeogenesis.pdf

1. a. Write out the two sequential

reactions catalyzed by Pyruvate

Carboxylase, giving names and

structures of reactants and products,

including the active site prosthetic

group. What is the nature and

significance of the linkage of the

prosthetic group to the Pyruvate

Carboxylase enzyme?


87

b. Describe and explain the significance

of the effect of acetyl coenzyme A on the

Pyruvate Carboxylase enzyme.

1- Why would it be

disadvantageous to the

organism to have Glycolysis

and Gluconeogenesis

operating simultaneously

within a cell? Briefly

describe one example of

reciprocal regulation of

Glycolysis and

Gluconeogenesis, involving

an allosteric regulator. For

the example chosen, write

out the reaction catalyzed

by the enzyme in each

pathway, and indicate the

nature of the effect of the

regulator (e.g., inhibition or

activation).

I- Short Questions:


gluconeogenesis pathway.

2- Enumerate the sources for

gluconeogenesis ?

3. Define futile cycle, relate it to

gluconeogenesis?

4- What are the irreversible reactions

unique to gluconeogenesis?

5- How many ATP are consumed for

synthesis of one molecule glucose

from 2 pyruvates


88

II- MCQ:

1- Gluconeogenesis is A. The formation of glycogen

B.The formation of starches

C.The formation of glucose from

noncarbohydrates

D.The formation of glucose from other

carbohydrates

2- Gluconeogenesis uses the same

enzymatic reaction of glycolysis

except for A. Pyruvate kinase

B.4 irreversible reactions in glycolysis

C.3 irreversible reactions in glycolysis

D.2 irreversible reactions in glycolysis

3- Any compound that can be

converted to _____can be a

precursor for gluconeogenesis. A. Citrate

B.Pyruvate

C.Oxaloacetate

D.b and c

III- True / False 1- Glucagon increases the

transcription of the gene for

PEP carboxykinase in

gluconeogenesis, while insulin

decreases it.

2- Fructose 2,6-bisphosphate is a

modulator that can stimulate

either glycolysis or

gluconeogenesis, depending on

cellular glucose concentrations.

3- At high glucagon concentrations

gluconeogenesis will be favored

over glycolysis.

4- The brain normally uses both

glucose and fatty acids as

energy sources.

5- Glycerol is one of the precursor

for gluconeogenesis.


89

LECTURE # (21 - 22) : Glycogen Metabolism


By the end of this lecture you

will be able to:

1-Define Glycogenesis and

Glycogenolysis , form a

working definition knowing the

substrates and products involved


produced.


Glycogenesis and

Glycogenolysis, particularly

tissues or cells in the body

where the pathway is most

important.

3- Locate the cell site of Glycogen

metabolism, where in the cell it

occurs (cytosol).

4- Describe the sequence of

events, the overall reaction

sequence and the number of

stages and reactions:

a. Material Flow:: Trace

the fate of labeled

carbon or other

Student Notes:

.


90

elements through the

pathway

b. Energy flow: Trace

the production and

consumption of ATP


production and

consumption of

reducing power.




branch points"


pathways and the reciprocal

regulation of both glycogenesis

and glycogenolysis

• Overview of Glycogen metabolism

• Structure and function of Glycogen

• Synthesis of Glycogen(Glycogenesis)

• Degradation of Glycogen (Glycogenolysis)

• Regulation of glycogenesis and Glycogenolysis.

• Glycogen storage diseases

Excess dietary glucose is stored as glycogen. Glucose can be rapidly and easily mobilized from glycogen, when the need arises; for example, between meals or during exercise. A constant supply of glucose is essential for life because it is the main fuel of the brain and the only


91

energy source that can be used by cells lacking mitochondria and by contracting skeletal muscle(during anaerobic glycolysis). Glycogen is therefore an excellent short – term storage material that can provide energy immediately.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 123 - 134


•

•

• You have the opportunity to watch the CD-ROM about Glycogen metabolism. You can access the CD-ROM during your spare time.

1- Glycogen metabolism http://web.indstate.edu/thcme/mwking/glycogen.html

2-Glycogen metabolism http://www.med.unibs.it/~marchesi/glycogen.html

3- Glycogen metabolism book http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.

chapter.2911

4- Glycogen metabolism animation http://www.wiley.com/college/fob/quiz/quiz15/15-

20.html

1- Describe the regulation of the

muscle Glycogen

Phosphorylase enzyme by

local allosteric regulators.


92

What is the effect of

phosphorylation of the enzyme

via Phosphorylase Kinase? A

diagram may be helpful. What

is the significance of the

allosteric regulation with

regard to cellular metabolism?

2.

a. Diagram and describe the

reaction cascade by which cyclic

AMP alters activity of the

Glycogen Phosphorylase enzyme.

(The process by which cyclic AMP

production is activated by

glucagon or epinephrine may be

omitted here.) Include the

effects of covalent modification

on sensitivity of Glycogen

Phosphorylase to allosteric

regulators. What is the

significance of such a regulatory

cascade in liver in relation to the

well being of the whole

organism?

b. How does the rise in cytosolic

[Ca++] that occurs during

activation of muscle contraction

affect glycogen breakdown? How

is this significant with regard to

metabolism during muscle

contraction?

1- Explain how genetic deficiency

of each of the following enzymes

leads to intracellular glycogen

accumulation (glycogen storage

disease) along with the specific

symptoms listed:

• Deficiency of Glucose-6-phosphatase in

liver, causing glycogen accumulation

plus hypoglycemia (low blood glucose)


93

when fasting.

• Deficiency of Glycogen Phosphorylase

in muscle, causing glycogen

accumulation plus muscle cramps with

exercise.

• Deficiency of Phosphofructokinase in

muscle, causing glycogen accumulation

plus inability to exercise.

I- Short Questions:

1- Give the cellular location of

Glycogen metabolism.

2- What are the main stores of

Glycogen in body ?

3. Enumerate the enzymes of

Glycogenesis and Glycogenolysis.

4- What is the advantage of branched

structure of glycogen.

5 – What is the difference between

glycogenolysis in liver and

muscles?

6- Enumerate Glycogen storage

diseases.

II- MCQ:

1- The enzyme which the key

regulatory step in glycogen

biosynthesis is

A. Glycogen synthase

B. Glycogenin

C. Branching enzyme

D. Phosphoglucomutase

2- Protein kinase A, which

stimulates glycogen

degradation, is activated

directly by A. Glucagon


94

B. Insulin

C. Epinephrine

D. Cyclic AMP

3- Glucose 1-phosphate formed by

glycogenolysis is converted to

glucose 6-phosphate by

phosphoglucomutase because

A. Glucose 6-phosphate is more stable

B. Glucose 6-phosphate is converted to

free glucose

C. Glucose 6-phosphate is an intermediate

in several pathways, including

glycolysis

D. Glucose 6-phosphate can be

transported to the liver

III- True / False 1- Enzymes to regulate glycogen metabolism are always active when phosphorylated by protein kineses. 2- Since caffeine inhibits cAMP

phosphodiesterase, too much

coffee can result in synthesis of too

much glycogen.

3-UDP-glucose is a precursor of

glycogen in all cells.

5- Glycogen storage disease

results in glycogen

accumulation in liver and

kidneys. It can be controlled

by changing ones diet.


95

LECTURE # (23) : Pentose phosphate pathway



able to:

1. Define the pentose phosphate

pathwaw , form a working




2- Trace tissue location of pentose

phosphate pathwaw, particularly

tissues or cells in the body where

the pathway is most important.

3- Locate the cell site of glycolysis,

where in the cell it occurs

(cytosol).



the number of stages and

reactions:

a. Material Flow:: Trace the

fate of labeled carbon or

other elements through the

pathway

b. Energy flow: Trace the

Student Notes:

.


96


of ATP



of reducing power




branch points"


pathways, with the emphasis on

the role of NADPH in other

biochemical pathways

• Overview of pentose phosphate

pathwaw

• Irreversible oxidative reactions

• Reversible nonoxidative reactions

• Uses of NADPH

• Glucose 6 – phosphate Dehydrogenase Deficiency

The pentose phosphate pathway occurs in the cytosol of the cell. The pathway provides a major portion of body's NADPH, which functions as a biochemical reductant. It also produces ribose 5- phosphate required for the biosynthesis of nucleotides.


97

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 143- 154


•

•

• You have the opportunity to watch the CD-ROM about pentose phosphate pathway. You can access the CD-ROM during your spare time.

1- Pentose phosphate pathway http://web.indstate.edu/thcme/mwking/pentose-

phosphate-pathway.html

2- Pentose phosphate pathway http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/m

b2/part1/pentose.htm

3- Pentose phosphate pathway (PowerPoint) presentation www.cwu.edu/~geed/543/Pentose%20Phosphate%20Pathway.ppt

4- Pentose phosphate pathway (poweeroint ) www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/15-pentose.ppt

1- Diagram and describe the

mechanism of the reaction

catalyzed by the enzyme

Transaldolase, including

structures of major

intermediates.

2. Write out the linear (oxidative)

portion of the Pentose Phosphate

Pathway, giving names and

structures of substrates and


98

reactants, and the name of each

enzyme. Summarize in words

what happens at each step. What

two products of the linear

portion of the Pentose Phosphate

Pathway have essential roles in

anabolic metabolism? What are

these roles?

Clinical Question

1- In male patients who are

homozygous for glucose 6-

phosphate dehydrogenase

(G6PD) deficiency,

pathophysiologic consequence

are more apparent in

erythrocytes (RBCs) than in

other cells, such as in the liver.

EXPLAIN.

I- Short Questions:


pentose phosphate pathway

2- What are the main products of

pentose phosphate pathway ?

3. Enumerate sources of NADPH?

4- What are the uses of NADPH in our

body. Enumerate? .

5 - What are the effects of glucose 6-

phosphate dehydrogenase

deficiency


99

II- MCQ:

1- The major regulatory step of the

pentose phosphate pathway is

catalyzed by which enzyme? A. transaldolase

B. phosphofructokinase-1

C. glucose 6-phosphate dehydrogenase

D. ribose 5-phosphate isomerase

2- The non-oxidative stage of the

pentose phosphate pathway

produces substances that are

intermediates of ___________. A. glycolysis

B. the citric acid cycle

C. the Cori cycle

D. glycogenolysis

3- Which is not a function of the

main products of the pentose

phosphate pathway?

A. To maintain the reduced form of iron in

hemoglobin.

B.To provide reducing power for the

synthesis of fatty acids.

C. To serve as precursors in the

biosynthesis of RNA and DNA.

D. To raise the concentration of cAMP.

III- True / False

1- Glucose 1,6-bisphosphate is

the primary starting substrate

for the pentose phosphate

pathway.

2- Two molecules of NADPH are

generated for each molecule of

glucose 6-phosphate that

enters the pentose phosphate

pathway.


100

3- Rapidly dividing cells generally

have a high pentose phosphate

pathway activity.

4- The enzyme transketolase

transfers 2-carbon units from

ketose phosphates to aldose

phosphates

5- NADH and pentose are the

main products of pentose

phosphate pathway


101

LECTURE # (24): Metabolism of Monosaccharides and

Disaccharides



be able to:

1- Define pathways for fructose,

Galactose and Lactose Metabolism ,

form a working definition knowing

the substrates and products involved


produced.

2- Trace tissue location of these

pathways, particularly tissues or

cells in the body where the pathway

is most important.

3- Locate the cell site of these

pathways, where in the cell it occurs

(cytosol).




a. Material Flow:: Trace

the fate of labeled carbon or other

elements through the pathway

b. Energy flow: Trace

the production and consumption of

Student Notes:

.


102

ATP


production and consumption of

reducing powerIdentify the Key

steps, either those which form major

control sites or those which are main

" branch points"


pathways especially Glycolysis

• Overview

• Fructose metabolism

• Galactose metabolism

• Lactose synthesis

Although many monosaccharides have been identified in nature, only a few sugars appear as metabolic intermediates or as structural components in mammals. The major source of fructose is sucrose, while the major dietary source of galactose is lactose, entry of both to cells is insulin - independent both can be metabolized for energy generation through glycolysis.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 135 – 142

2. Supplementary Texts And Resources:

Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby


103

•

•

• You have the opportunity to watch the CD-ROM about Monosaccharide metabolism. You can access the CD-ROM during your spare time.

1- Fructose Metabolism http://www.gpnotebook.co.uk/cache/1798635578

m 2-Fructosa Web site http://www.drkaslow.com/html/fructose.html 3- Fructose and Galactose Metabolism http://web.indstate.edu/thcme/mwking/non-glucsugar-metabolism.html 4- Galactose Metabolism http://www.gpnotebook.co.uk/cache/1899298874.htm

Describe, how different monosaccharides

can be interconverted, Explain the

benefits of this interconversion to body

metabolism.


A newborn baby experienced

abdominal distension, severe

bowel cramps, and diarrhea

after being fed milk. A

hydrogen analysis of his

exhaled breath discovered an

eighty – fold increase in the

production of H2 ninety

minutes after milk feeding.

a- Explain the case


104

b- This condition is

preventable or not?

2- Clinical Case

A galactosemic female is able

to produce lactose, How?

I- Short Questions:

1- What is the main source of dietary

fructose?.

2- What is the main source of dietary

galactose?.

3. Although fructose is more sweaty

than Glucose it is not

recommended to be an exchange

to it in our diet

4- What is the effects Galactokinase

deficiency.

5- Define fructosuria, what is its

cause.

II- MCQ:

1- 1- Which is an intermediate

formed in the conversion of glucose

to fructose? A. glucose-1-phosphate

B. sorbitol

C. ribose

D. aldose reductase

2- What types of reactions are

involved in the two-step conversion

of glucose to fructose?

A. reduction followed by oxidation

B. two sequential hydrolysis reactions

C. hydrolysis followed by isomerization

D. phosphorylation followed by


105

dephosphorylation

3- What is a cause of cataracts in

the eye lens of individuals with

diabetes?

A.Accumulation of sorbitol and protein

precipitation in the lens.

B. Precipitation of glucose not oxidized

by glycolysis in the lens.

C. The absence of membrane transport

proteins for pyruvate in the lens cells.

D. Lack of regulation of gluconeogenesis

in the lens and the accumulation of

fructose.

IV- True / False

1- Lactose is the main source

of dietary fructose. 2- Absorption of fructose is insulin

dependent.

3- Aldose reductase reduces glucose, producing sorbitol

4- Classic galactosemia results from

missing of Galactose kinase

5- Lactose is synthesized by lactase synthase from UDP glucose and Galactose.


106

LECTURE # (25) : Fatty acid oxidation


By the end of this lecture you will be able to:

1- Sequence the reactions catalyzed by acyl-CoA synthetase, carnitine palmitoyl transferaseI,carnitine-acylcarnitine translocase, and carnitine palmitoyl transferaseII.

2- Indicate which of these enzymes is regulated by malonyl-CoA.

3- Explain the importance of carnitine for the oxidation of long-chain fatty acid but not short- and medium-chain fatty acids.

4- Discuss the steps of beta oxidation of fatty acids.

5- Explain the importance of citric acid cycle for the oxidation of fatty acids .

6- Calculate the yield of ATP that is formed through the complete oxidation of one mole of palmitic acid.

7- Indicate the roles of long chain-, medium chain- and short chain-acyl CoA dehydrogenases in the oxidation of long chain fatty acids. Explain why a defect in the medium chain enzyme results in excretion of dicarboxylic acids and acyl carnitine esters in the urine.

Student Notes:

.


107

• Tissues that are most active in oxidation of fatty acids and its sub cellular location

• Conditions which favor the process of oxidation of fatty acids

• Role of carnitine in the process of beta oxidation

• The difference in oxidation of long, medium and short chain fatty acids

• The steps of beta oxidation

• Energy gained of beta oxidation

• Regulation of beta oxidation

• The other types of fatty acid oxidation

• Diseases associated with genetic abnormality of fatty acid oxidation

Beta oxidation takes place in fed state in certain tissues as a source of energy, in starvation it is stimulated to provide energy for many tissues as liver (which becomes completely dependent on it as a source of energy.

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey. (187-193)

2. Supplementary Texts And Resources: Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby. (pp 169-173)

•

•

• You have the opportunity to watch the CD-ROM about fatty acid oxidation. You can access the CD-ROM during your spare time.


108

1-http://www.dentistry.leeds.ac.uk/biochem/thcme/fatty-acid-oxidation.html 2-

http://www.biocarta.com/pathfiles/betaoxidationPathway.asp

3-

http://ull.chemistry.uakron.edu/Pathways/b_oxidation/index.html 4-

http://www.biocarta.com/pathfiles/boxnpPathway.asp

5-

http://www.biocarta.com/pathfiles/h_cptPathway.asp

6-

http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.html 7-

http://www.biocarta.com/pathfiles/oddnumberchainPathway.asp

8-http://www.biocarta.com/pathfiles/polyunsatfattyacidPathway.asp

1- Try to explain the sequence of

events that takes place in the mitochondria during beta oxidation of fatty acid

2- Write down how beta oxidation is regulated

1- Clinical Question: In diabetic

patient type I, do you expect that beta oxidation of fatty acid to be increased, decreased or normal and why?

2- Clinical Case: A three month old baby brought to you by his mother, she was complaining that the baby seemed to be lethargic and does not grow well, and he


109

was on breast fed only. What possible reason(s) may be the cause of this condition?

I- Short Questions:

a) Name the different types of oxidation of fatty acid

b) List the difference between fatty acid synthesis and beta oxidation regarding hydrogen carrier used and the site they occur

II- MCQ: 1- Two high energy bonds are lost during

β oxidation of long chain fatty acids in:

a) Transport of acyl carnitine inside the mitochondria

b) Formation of acyl CoA inside the mitochondria

c) Formation of acyl CoA in the cytoplasm

d) Release of acetyl CoA from acyl CoA by the action of thiolase enzyme

e) Non of the above 2- All the following are intermediate in β-

oxidation except:

a) FADH

b) NADPH

c) NADH

d) Acetyl CoA

e) All of the above

III- True / False a- The major type of fatty acid

oxidation in most of he tissues is omega oxidation

b- Beta oxidation takes place in all tissues

c- Compared to carbohydrate oxidation of fatty acids generate smaller quantity of ATP


110

LECTURE # (26) : Fatty acid synthesis



1- Identify the substrate for the building of fatty

acid and where it is made. Explain how this substrate is transferred to the cytoplasm.

2- Describe the importance of glycolysis in the cytosol for fatty acid synthesis.

3- Discuss how the fatty acid synthase enzyme complex works.

4- Explain how stearic acid and oleic acid are synthesized from palmitic acid and in what regions of the cell they are synthesized.

5- Describe the different mechanisms of short-term control of the formation of fatty acids.

6- Indicate the roles of insulin and glucagon in the regulation.

9- Describe long-term control (enzyme induction) of the formation of fat. Indicate the enzymes that are subject to long term control.

10-Explain what prevents the liver from oxidizing fatty acids at the same time it is synthesizing fatty acids.

• Tissue and subcellular location for

fatty acid synthesis

• Transport of the building block for

Student Notes:

.


111

fatty acid synthesis from the mitochondria to the cytoplasm

• The generation of the substrates for fatty acid synthesis in the cytoplasm

• The arrangement and structure of fatty acid synthesase enzyme

• Energy requirement for fatty acid synthesis

• Regulation of fatty acid synthesis

• Elongation and unsaturation of fatty acid

Fatty acid synthesis is an anabolic process, so it is favored during the fed state and inhibited during starvation through hormonal regulation which also activates fatty acid oxidation, so during starvation fatty acid synthesis is shut down and oxidation is turned on. Acetyl CoA is the substrate for fatty acid synthesis which is produced in the mitochondria and has to be transported to the cytoplasm in the form of citrate. In the cytoplasm the other requirement for fatty acid synthesis are present (NADPH and fatty acid synthesase complex)

1. Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey. (pp 179-186)


•

•

• You have the opportunity to watch the CD-ROM about fatty acid synthesis You can access the CD-ROM during your spare time.


112

1- http://ull.chemistry.uakron.edu/Pathways/FA_synthesis/index.html#

2- http://www.genome.ad.jp/kegg/pathway/map/map00561.html

3- http://ull.chemistry.uakron.edu/Pathways/FA_synthesis/index.html

4- http://ull.chemistry.uakron.edu/genobc/Chapter_24/ 5- http://www.uic.edu/depts/mcam/mcbc/lect_2004/lecture_27.pdf

1- Outline and contrast the processes

of fatty acid synthesis and oxidation 2- Write down the source(s) of each of

the substrate for fatty acid synthesis

1- Clinical Case

Obesity, which will be covered

in the tutorial.

I- Short Questions:

a) Name the key regulatory enzyme in fatty acid synthesis

b) Using a diagram drew how this enzyme is controled


113

II- MCQ: 1- Acetyl groups for fatty acid synthesis is

derived mainly from:

a) Only glucose

b) Ketogenic amino acids only

c) Beta oxidation of fatty acid

d) Glucose and amino acids

e) Non of the above 2- Acetyl CoA for fatty acid synthesis is

produced in the cytoplasm by the action of:

a) Acetyl CoA synthetase

b) Citrate lyase

c) Pyruvate dehydrogenase

d) Thiolase

e) Non of the above

II- True / False

a) The synthesis of fatty acids occurs in the cytoplasm of the cells

b) The key regulatory enzyme in

fatty acid synthesis is the fatty acid synthesase

c) Insulin hormone inhibits fatty

acid synthesis

d) Citrate lyase enzyme has no role in the process of fatty acid synthesis


114

LECTURE # (27,28) :

Lipogenesis



able to:

1. Define lipogenesis and its

importance

2. Locate the important sites

(tissues) for lipogenesis and its

intracellular location

3. Discuss the favorable conditions

for lipogenesis

4. Differentiate between lipogenesis

in adipose tissues and other tissues

and explain this differences

5. Trace the substrate of lipogenesis

to its final product

• Overview and definition of

lipogenesis

• Sites of lipogenesis (tissues and subcellular level)

• Substrates for lipogenesis

• Energy utilization of lipogenesis

• Regulation of lipogenesis

• Fed and fasting conditions and their effect on lipogenesis

Student Notes:

.


115

How excess calorie are stored in the form of

triglycerides and how this process utilizes

excess CHO and protein for its synthesis to be

utilized during fasting and starvation

conditions.



•

•

• You have the opportunity to watch the CD-ROM about lipogenesis. You can access the CD-ROM during your spare time.

1- http://www.lipidsonline.org/ 2- http://ull.chemistry.uakron.edu/Pa

thways/FA_synthesis/index.html# 3- http://www.genome.ad.jp/kegg/pa

thway/map/map00561.html 4- http://www.biochem.arizona.edu/c

lasses/bioc801/power/lec27.ppt#256,1,Slide 1

5- http://www.genome.jp/kegg/pathway/map/map01130.html

6- http://www.biocarta.com/pathfiles/h_vobesityPathway.asp


116

1. Explain why the liver is able to utilize free

glycerol for the synthesis of triglyceride

glycerol, but the adipose tissue must have

glucose in order to synthesize glycerol

3-phosphate. Give the reaction catalyzed by

the enzyme missing in the adipose cell.

2. Write down the role of insulin in

lipogenesis

Clinical Question:

1. What is BMI and how it is used

for classification of obesity?

Clinical Case:

2. Obesity, which will be covered

in the tutorial.

I- Short Questions:

1- State the tissues and the subcellular

location of lipogenesis

2- Outline the major difference (s) between

lipogenesis in the liver and that in the

adipose tissue

III- MCQ:

1- In liver lipogenesis, glycerol 3-

phosphate can be obtained by:

a)The action of glycerol

kinase enzyme only

b) Through glycolysis

intermediates only

c)Both of the above

d)Non of the above


117

2- Adipocytes contain fat droplets which

serve to provide to an animal

a)Increased cell volume

b) Insulation

c) provide energy

d) a and b

e) b and c

III- True / False a. Lipogenesis takes place in

the cytoplasm of the adipose tissues and the liver

b. Glycerol kinase is very active enzyme in lipogenesis in the adipose tissue

c. Lipogenesis is stimulated by insulin and inhibited by glucagons


118

LECTURE # (29) : Ketone bodies metabolism



1- Define what is meant by ketogenesis and ketolysis

2- Enumerate the different ketone bodies

3- Evaluate the process of synthesis of ketone bodies

4- Explain the role of the liver in ketogenesis

5- Explain why ketone bodies synthesis is activated during fasting and starvation

• Definition of ketogenesis and

ketolysis

• The central role of the liver in ketogenesis and its inability to utilize them

• The steps of ketogenesis in the liver

• The steps of ketolysis in extra hepatic tissues

• Regulation of ketogenesis and ketolysis

•

•

•

Student Notes:

.


119

Remember that ketone bodies are used as a major source of energy during starvation in most of the tissues even the brain to decrease the process of gluconeogenesis from muscle protein and spare the glucose produced from gluconeogenesis mainly to the brain and for the tissues which do not have mitochondria such as RBCs.



•

•

• You have the opportunity to watch the CD-ROM about fatty acid oxidation. You can access the CD-ROM during your spare time.

1- http://www.biocarta.com/pathfiles/ketonebodiesPathway.asp

2- http://ull.chemistry.uakron.edu/genobc/Chapter

_24/ 3- http://ull.chemistry.uakron.edu/Pathway

s/ketone_bodies/index.html

1- Draw the steps of ketogenesis

indicating the steps during which


120

CoA-SH is regenerated 2- Drew a graph connecting both beta

oxidation and ketogenesis

1- Clinical Question:

a) In type I diabetes, ketone bodies tend to increase more than type II, explain why?

2- Clinical Case: A type I diabetic

patient delivered to you in a coma in the ER , his blood glucose level was 500 mg/dl (27.8 mmol/L), his breath had the acetone charachtristic odour. a) What other investigation(s)

would you like to do? b) What type of coma is it? c) What is the biochemical bases

of this coma?

I- Short Questions: 1- Explain why ketogenesis is essential for energy production in the liver during starvation 2- Explain why the liver can not utilize ketone bodies

II- MCQ: 1- Regarding ketogenesis and ketolysis:

a) Ketogenesis takes place in the mitochondria of extrahepatic tissues while ketolysis in the cytoplasm of extrahepatic tissues

b) Ketolysis takes place in the cytoplasm of extrahepatic tissues

c) Ketogenesis and ketolysis takes place in liver mitochondria

d) Ketogenesis takes place in liver mitochondria only


121

e) All of the above 2- Regeneration of CoA-SH takes place

during ketogenesis in the step (s) of:

a) formation of acetoacetyl CoA

b) formation of beta hydroxybutyrate from acetoacetate

c) formation of hydroxymethylglutaeyl (HMG) CoA

d) Both (a) and (c)

e) All of the above

III- True / False 1- Ketogenesis takes place in all the

tissues 2- Ketone body oxidation is the major

source of energy for most of the tissues in the absorptive state

3- Ketogenesis takes place in the cytoplasm of the liver only


122

LECTURE # (30) : Lipolysis



1- Define lipolysis 2- Locate the site where it happens in he tissue

and the subcellular location 3- Explain the importance of this pathway in

case of fasting and most important during

starvation 4- Trace the starting substrate to its final fate 5- Discuss how this pathway is tightly regulated

• Definition of lipolysis

• Conditions favoring lipolysis

• Site and subcellular level

• The importance of lipolysis for energy providing

• HSL and its regulation

• The effect of fed, fasting and exercise conditions on lipolysis

Remember that TG is the major energy store in your body, the calorie content of TG in adipose tissue is about 120000, those calories are mobilized through the process of lipolysis during starvation to provide energy in the form of free fatty acid for oxidation in most

Student Notes:

.


123

of the tissues especially the liver and muscles.


2. Supplementary Texts And Resources: Medical Biochemistry, Baynes and Dominiczek, 1st edition, Mosby.

•

•

• You have the opportunity to watch the CD-ROM about lipolysis. You can access the CD-ROM during your spare time.

1- http://www.wiley.com/legacy/college/bo

yer/0470003790/animations/fatty_acid_metabolism/fatty_acid_metabolism.htm

2- http://www.elmhurst.edu/~chm/vchembook/620fattyacid.html

3- http://www.webpages.uidaho.edu/~dcole/Lipids

%20Lecture%2012.pdf

1- Draw how HSL is hormonally

regulated

1- Clinical Question a) Can you explain why the

marathon runner is fed during the marathon in such a ay that his blood glucose is kept low

2- Clinical Case a) A patient was delivered to the ER


124

with history of type I DM and he was in coma and you diagnosed him as diabetic keoacidosis coma, what do you expect about his plasma level of free fatty acid (low, normal or high) and why?

I- Short Questions:

1- Define lipolysis and mention where it happens

IV- MCQ: 1-Regarding lipolysis

a) It is mostly active during fed state

b) It takes place in the adipose tissue and the released fatty acids are carried by chlomicrons to peripheral tissues for oxidation during fasting condition

c) It is stimulated by insulin

d) The released fatty acids are carried and transported to peripheral tissues by plasma albumin

e) All of the above 2-Regarding hormone-sensitive lipase:

a) It is active in the dephosphorylated form

b) It is activated by the action of the insulin hormone

c) It is activated through the action of c-AMP dependent protein kinase

d) Its activity is maximum during the fed state

e) Non of the above

V- True / False 1- Lipolysis means the

mobilization of energy storage in adipose tissue in the form of ketone bodies


125

2- HSL is the key regulatory enzyme in lipolysis

3- Glucagon hormone stimulates the process of lipolysis while it is inhibited by insulin


126

PRACTICALS

Practical (1) : Enzymes: Amylase activity in serum

Department: Biochemistry

Teaching location: Classroom

By the end of this practical the student will be able to:

o Determine the optimum temperature for enzyme activity

o Estimate serum amylase activity in the provided sample

o Explain the function of serum amylase

o Discuss the diagnostic importance of serum amylase

• Determination of serum amylase

• Explaining the effect of temperature on enzyme activity

• Discuss the role of measurement of serum amylase in disease condition

• Evaluating the role of amylase in GIT digestion of nutrients

Transferable skills:

• Interrelate laboratory data with clinical findings

READING: Laboratory Handouts will be distributed


127

Practical (2) : Enzymes: Estimation of serum alkaline phosphatase




o Determine serum alkaline phosphatase

o Evaluate the effect of enzyme inhibitors on enzymatic activity

o Define Km and Vmax

o Show how the Lineweaver-Burk plot can be used to evaluate Km and Vmax

• Determination of serum alkaline phosphatase

• The definition of Km and Vmax and the effect of enzyme inhibitors on both of them

• Plotting of Lineweaver-Burk plot and its utilization for evaluation of Km and Vmax

• Clinical importance of measurement alkaline phosphatase



• Serum alkaline phosphatase as marker for bone and liver diseases



128

Practical (3) : Enzymes: Serum CK isoenzymes


Teaching location: Classrooة


o Define what is meant by isoenzymes

o Separate the different CK isoenzymes using electrophoresis

o Evaluate the role of CK in tissues

o Discuss the role and importance of measuring CK isoenzymes in different diseases conditions

• Separation of serum CK isoenzymes

• Function of Ck in different tissues

• The different isoenzymes of CK and relation to different diseases



• How to use CK isoenzymes in evaluating cardiac and muscle diseases



129

Practical (4): Biologic Oxidation. Oxidative phosphorylation and effect of uncouplers



By the end of this practical the you will be able to:

o Determine the amount of inorganic phosphate consumed in the process of oxidative phosphrylation

o Explain the effect of uncouplers on this phosphrylation

o Discuss how glycolysis was inhibited in this reaction

• Determination of activity of the process of oxidative phosphrylation

• Explaining the effect of uncouplers

• Differentiation between the mechanism of action of different types of uncouplers


• Interrelate laboratory result with some drugs used as uncouplers



130

Practical (5) : Serum lactate




o Determine blood lactate

o Evaluate the importance of determination of serum lactate

o To discuss how one enzyme affects different metabolic pathways

• Determination of serum lactate

• The importance of measurement blood lactate in evaluating children with hypoglycemia

• The relation of lactic acidosis to enzyme deficiency such as glucose 6-phosphatase deficiency





131

Practical (6) : Serum lactate dehydrogenase isoenzymes




o Use electrophoresis for separation of LDH isoenzymes

o Differentiate between the different LDH isoenzymes (sources and function)

o Evaluate the role of LDH isoenzyme in disease diagnosis

• Determination of serum LDH isoenzymes using cellulose electrophoresis

• The role of LDH in different metabolic pathways

• The sources of LDH isoenzymes and its role in diagnosis



• How to use LDH isoenzymes in evaluating cardiac cases



132

Practical (7) : OSPE TRAINING




o Be familiar with the OSPE

• 8-9 stations will be included, two of them will be related to the previously mentioned tests (determination of the analytes), the other will include questions to evaluate the student benefits of the information given in these practicals.


• Accuracy of performing the test

• Utilization of data in the different stations for interpretation of clinical cases



133

Practical (8) : Liver glucose-6-phosphatase deficiency




o Determine glucose-6-phosphatase in tissue extract

o Discussing the different changes in blood glucose, lactate, pyruvate, fatty acids, ketone bodies and uric acid found in this case

o Explaining the basis of other glycogen storage diseases

• Determination of glucose-6-phosphatase activity in liver tissues



• Correlation of lactic acidosis with glucose-6-phosphatase deficiency



134

Practical (9) : Plasma glucose estimation




o Estimate plasma glucose

o Differentiate between the different methods for measuring plasma glucose

o Utilize the result of plasma glucose to diagnose a case of hyperglycemia

o Discuss how to monitor a diabetic patient

• Determination of plasma glucose

• Difference between blood glucose and plasma glucose

• WHO classification of hyperglycemia



• How to utilize plasma glucose for diagnosis and monitoring diabetic patients



135

Practical (10) : Oral glucose tolerance curve




o Draw glucose tolerance curve

o Utilize this curve in diagnosis of hyperglycemic case

o Differentiate between the different responses in this test

• Drawing the curve using different glucose concentration

• Estimation of the different samples (fasting, 60 minutes, 90 minutes and 120 minutes)

• The difference between oral glucose and intravenous glucose tolerance curve

• Monitoring of diabetic patient



• How to utilize plasma glucose for diagnosis and monitoring diabetic patients



136

Practical (11) : Lipid: Estimation of plasma total cholesterol




o Estimate plasma cholesterol using cholesterol oxidase method

o Correlate plasma cholesterol level with cardiac diseases

o Utilize biochemical knowledge in treating this patient

• Measurement of plasma total cholesterol

• Different types of hyperlipidemia

• Classification of hypercholesterolemia according to Adult Treatment Panel III (ATP III) provided by National Cholesterol Education Program (NCEP)



• Approach a case of hypercholesterolemia



137

Practical (12) : Lipid: Estimation of plasma Triacylglycerol




o Estimate plasma triacylglycerol

o Evaluate the role of lipoprotein lipase in lipid metabolism

• Differentiate between the different types of hyperlipidemia

• Measurement of plasma triacylglycerol

• Different types of hyperlipidemia

• Classification of hyperlipidemia according to Adult Treatment Panel III (ATP III) provided by National Cholesterol Education Program (NCEP)

•



• Approach a case of hyperlipidemia



138

Practical (13) : Lipid: Estimation of fecal fat




• Estimate fecal fat

• Discuss lipid absorption and factors affecting absorption

• Discuss malabsorption as a defective in digestion or absorption

• Estimation of fecal fat

• Interference of pancreatic damage with the utilization of dietary fat

• State of digestion and absorption of other macronutrients in this case

• Different causes that may be encountered in this case for malabsorption


• How to approach a case of steatorrhoea



139

Practical (14) : OSPE TRAINING




o Be familiar with the OSPE

• 8-9 stations will be included, two of them will be related to the previously mentioned tests (determination of the analytes), the other will include questions to evaluate the student benefits of the information given in these practicals.


• Accuracy of performing the test

• Utilization of data in the different stations for interpretation of clinical cases



140


141

PBL process

• The clinical scenario

• Key information

• Explore the problem

• What you know

• What you need to know

• Identify learning issues

• Self/group study

• Share the knowledge

• Solve the problem

• Give feedback & reflect


142

Tutorial # 1

Paget’s Disease of Bone

� Introduction During this week you will work through the case of a Paget’s Disease of Bone

A 74-year old woman presented with a 6-week history of pain localized to the left buttock.

It did not radiate down the lateral aspect of her thigh and was not aggravated by stooping.

On examination there was full movement of both hip joints and no limitation of forward

flexion or extension or lateral rotation. The left buttock was slightly warmer to touch than

the right. Her blood pressure was 160/75 mmHg and pulse 84/min.

Clinical investigations

Plasma Reference Range

Urea 5.0 mmol/L 25-7.0

Albumin 39 g/L 27-42

Calcium 2.32 mmol/L 2.15-2.55

Phosphate 1.12 mmol/L 0.60-1.40

ALP 955 U/L 90-250

Radiological examination demonstrated extensive Paget’s disease of the pelvis, sacrum and

left femur


143

By the end of this tutorial the student will be able to:

1. Interpret biochemical abnormalities in clinical cases

2. Comment on the clinical and biochemical findings

3. Learn the diagnostic value of different isozymes

4. Learn the clinical application of enzymes assay in clinical conditions

1. How would you interpret the biochemical investigations?

2. What is the most probably diagnosis of this case? Why?

3. What is the clinical application of ALP assay in such a clinical situation?

4. What is the diagnostic value of different isozymes?

1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey


Try to access CD-ROM series about enzymes.

1. http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html

2. http://www.pagetsdisease.com/info/about/diagnosed.jsp?usertrack.filte

r_applied=true&NovaId=2229644978497118671

3. http://www.mountauburn.caregroup.org/body.cfm?xyzpdqabc=0&id=

6&action=detail&AEProductID=HW_Knowledgebase&AEArticleID=

hw1717&AEArticleType=MedicalTest


144

Learning issues

At the end of the first session you will be able identify the learning issues which

related to the Paget’s Disease of Bone

Try to summarize these learning issues in the table below. We recommend you to

learn about these issues. This will help you to solve the problem in the next

session.

Learning issues Notes

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145

Tutorial # 2

Chest Pains

� Introduction During this week you will work through the case of chest pain

You are in charge of a coronary care unit. The previous day, there were 2 admissions via

the accident and emergency services of patients with suspected MI. both men were in their

late 40's and had suffered intense chest pain. Patient (a), a businessman, had been taken ill

at a local restaurant, while patient (b), a teacher, had just returned home after a strenuous

jogging session. Tow blood samples had been taken from each patient, at ≈ 10hr and 24hr

after the onset of chest pains, for assay of serum CK and LDH.


Patient (A) Patient (B) Plasma

10hr 24hr 10hr 24hr

Reference Range

Total CK 748 850 735 790 20-150 U/L

CK-MB 82 75 25 23 0-3 U/L

LDH 129 182 106 167 45-90 U/L


146




3. Learn the diagnostic application of cardiac enzymes in heart patients

4. Learn the use of anticoagulant therapy in MI

1. How would you interpret the changes in cardiac enzymes in both patients?

2. Did the results of biochemical tests assist in making the diagnosis?

3. Would screening the population at large for serum enzymes such as CK and

LDH be of predictive value in identifying people at risk of heart attack?

4. One of the treatments that may be given in this situation is the IV

administration of t-PA. What is the basis of this treatment?



Try to access CD-ROM series about Enzymes

1. http://en.wikipedia.org/wiki/Myocardial_infarction

2. http://www.guideline.gov/summary/summary.aspx?doc_id=6534

3. http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm


147

• Learning issues


related to chest pain cases.



session.


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148

Tutorial # 3

Alcohol-Induced Cirrhosis of The Liver

� Introduction During this week you will work through the case of Alcohol-Induced Cirrhosis of

The Liver

A 75-year old woman was admitted to hospital following the sudden onset of a right-

sided hemiparesis. She had a history of epilepsy and was on treatment with phenytoin.

Clinical examination confirmed a right-sided weakness; her blood pressure was normal.

Her speech was slurred and her breath smelt strongly of alcohol.


Plasma Reference Range

Bilirubin 12 μmol/L <21

ALP 275 U/L 21-92

GGT 402 U/L 6-32

AST 34 U/L 6-35

Ethanol 133 mg/dl

Phenytoin 46 μmol/L 40-80


149




3. Learn the changes of plasma enzymes activities in liver diseases

1. How would you interpret the biochemical investigations?

2. What is the most probably diagnosis of this case? Why?

3. What is the clinical application of ALP assay in such a clinical situation?

4. What are the change patterns of plasma enzymes in liver diseases?



Try to access CD-ROM series about Enzymes

1. http://www.healthsystem.virginia.edu/uvahealth/adult_liver/alcohol

.cfm

2. http://www.umm.edu/liver/alcohol.htm

3. http://www.liverfoundation.org/education/info/alcohol/

4. http://www.clevelandclinicmeded.com/diseasemanagement/gastro/a

ld/ald.htm


150

• Learning issues


related to Alcohol-Induced Cirrhosis of The Liver



session.


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151

Tutorial # 4

Genetic defect in the Pyruvate Dehydrogenase Complex

� Introduction During this week you will work through the case of a Genetic defect in the

Pyruvate Dehydrogenase Complex

By the end of this tutorial you will be able to:

1. Name the enzyme components of pyruvate dehydrogenase complex and

cofactors needed for it.

2. Explain the high plasma concentrations of pyruvate, lactate and alanine in a

case with defect in pyruvate dehydrogenase complex.

3. Recognize the rationale for attempting therapy with thiamine, biotin,

bicarbonate, and protein restriction.

4. Explain why restriction of dietary carbohydrate may not be useful in

treating a patient with genetic defect in pyruvate dehydrogenase complex.

1. What are the enzyme components of pyruvate dehydrogenase complex?

And what are the cofactors needed for it?

A full-term male infant failed to gain weight, had episodes of vomiting, and showed

metabolic acidosis in the neonatal period. A physical examination at 8 months showed

failure to thrive, hypotonia, small muscle mass, severe head lag, and a persistent acidosis,

pH 7 to 7.2. Blood lactate (9 mmol/L), pyruvate (2.4 mmol/L), and alanine (1.36 mmol/L)

were greatly elevated. Since these symptoms suggested a genetic defect in pyruvate

metabolism, treatment with thiamine, biotin, bicarbonate, protein restriction, and a

ketogenic diet were all tried, but none of the treatment alleviated the lactic acidosis. After

informed consent, oral lipoic acid greatly improved the lactic and pyruvic acidemia.The

patient was doing well 2 years later.


152

2. Why were the plasma concentrations of pyruvate, lactate, and alanine

abnormally high?

3. What was the rationale for attempting therapy with thiamine, biotin,

bicarbonate, and protein restriction?

4. Restriction of dietary carbohydrate to 40% of the food calories has been

fairly effective in alleviating the symptoms of lactic acidosis in patients in

whom the genetic defect in the pyruvate dehydrogenase complex is

presumably in the E1 subcomplex. In this patient it caused a worsening of the

acidosis. Suggest an explanation.

1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 107 - 114


Try to access CD-ROM series about carbohydrate metaboliosm.

1. www.valuemd.com/usmle-step-1-forum/21747-high-yield-biochemistry

2. watcut.uwaterloo.ca/webnotes/PDF/MeatbolismNotes.pdf

3. www.answer.com/topic/pyruvate-dehydrogenase-complex-deficiency

4. www.wikipedia/wiki/pyruvate dehdrogenase complex defect


153

• Learning issues


related to the genetic defect in the Pyruvate Dehydrogenase Complex



session.


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156

Tutorial # 5

Pyruvate carboxylase deficiency (Dysfunction of Krebs’ cycle) � Introduction During this week you will work through the case of a Pyruvate carboxylase

deficiency (Dysfunction of Krebs’ cycle)


1. State the reaction catalyzed by pyruvate carboxylase enzyme.

2. Name the subcellular site of pyruvate carboxylase.

3. Contrast the major biosynthetic function of krebs’ cycle in brain and its main

catabolic function in other tissues as skeletal muscle and heart.

4. Relate the failure of alanine load to induce gluconeogenesis in patients with

pyruvate carboxylase deficiency.

5. Conclude the benefit of glutamine in stimulation the growth of fibroblasts from

a patient with pyruvate carboxylase deficiency disease.

6. Explain the lipid accumulation in cultured fibroblasts in patients with pyruvate

carboxylase deficiency.

7. Interpret the use of glutamic acid and aspartic acid in therapy of pyruvate

carboxylase deficiency.

1. What reaction is catalyzed by pyruvate carboxylase? Where is the enzyme

located in cells?

A 3-month-old female seemed normal until she developed seizures. The infant became

progressively worse, showing hypotonia, psychomotor retardation, and poor head control.

She had lactic acidosis and an elevated plasma pyruvate level, both more than seven times

the normal amount. Plasma alanine concentration was high, and an alanine load failed to

induce a normal gluconeogenic response. Pyruvate carboxylase activity was measured

using extracts of cultured skin fibroblasts and was found to be less than 1% the normal

level. Fibroblasts from the patient accumulated five times greater than normal amounts of

lipid.


157

2. What is the metabolic function of pyruvate carboxylase?

3. Explain the failure of the alanine load to induce gluconeogenesis in the

patient.

4. Why did lipids accumulate excessively in the patient’s fibroblasts?

5. What treatment would you suggest for a patient with this disease?




١. www.emedicine.com/Med/topic 1967.htm

2. children.webmd.com/Pyruvate_Carboxylase_deficiency

3. www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?di=226150

4. www.answer.com/topic/pyruvate-carboxylase-deficiency


158

• Learning issues


related to the genetic defect in the Pyruvate carboxylase deficiency Try to

summarize these learning issues in the table below. We recommend you to learn

about these issues. This will help you to solve the problem in the next session.


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159

Tutorial # 6

Von Gierke’s disease

� Introduction During this week you will work through the case of a Von Gierke’s disease

The patient was a 12-year-old girl who had a grossly enlarged abdomen. She had a history

of frequent episodes of weakness, sweating, and pallor that were eliminated by eating. Her

development had been somewhat slow. Her physical examination revealed the following:

Blood pressure 110/58 mmHg

Temperature 38 ºC

Weight 22.4 kg (low)

Height 128 cm (low)

Lungs clear

Heart normal

Abdomen prominent with slight venous distention

Liver masssively enlarged, firm and smooth

Spleen & Kidneys not palpable

The following are laboratory findings for a fasting blood sample:

Patient Normal values

Glucose (mmol/L) 2.8 3.9 – 5.6

Lactate (mmol/L) 6.6 0.56 – 2.0

Pyruvate (mmol/L) 0.43 0.05 – 0.10

Free fatty acids (mmol/L) 1.6 0.3 – 0.8

Triglycerides (g/L) 3.15 1.5

Total ketone bodies (mg/L) 400 30

pH 7.25 7.35 – 7.44

Total CO2 (mmol/L) 12 24 - 30

A liver biopsy specimen revealed bulging and dilated hepatic cells, the portal areas were

compressed and shrunken, and no inflammatory reaction.. Glycogen content was 11g/100 g

of liver (normal up to 8%), and lipid content was 20.2 g/100 g of liver (normal less than

5g). Hepatic glycogen structure was normal.

The following are results of enzyme assays performed on the liver biopsy tissue:

Enzyme Patients (units per Normal range

gram of liver N) (units per gram of liver N)

Glucose-6- phosphatase 22 214 ± 45

Glucose-6- phosphate dehydrogenase 0.07 0.05 ± 0.13

Phosphoglucomutase 27 25 ± 4

Phosphorylase 24 22 ± 3

Fructose- 1,6 bisphosphatase 8.4 10 ± 6


160


1. Describe the normal structure of hepatic glycogen.

2. Name the enzyme defect in Von Gierke’s disease.

3. Outline the tissues that might be expected to accumulate excessive amounts

of glycogen in Von Gierke’s disease.

4. Match the changes in this structure if there is deficiency in branching

enzyme.

5. Explain the reasons for the fasting hypoglycemic episodes in Von Gierke’s

disease.

6. Relate the elevated free fatty acids, ketonemia and metabolic acidosis in

this disease.

7. Predict and explain the result of continuous parenteral feeding.

8. Recognize the nature of acidosis and its causes in a case of Von Gierke’s

disease.

1. What is a normal structure for hepatic glycogen?

2. What changes in this structure would accompany a deficiency in branching

enzyme?

3. Which other tissues might be expected to accumulate excessive amounts of

glycogen?

4. Explain the reasons for the fasting hypoglycemic episodes.

5. To what might be ascribed (a) the elevated free fatty acid, (b) the

ketonemia, and (c) the metabolic acidosis?


161

6. What would you predict would be the result of continuous parenteral

feeding? Explain.

7. What is the nature of acidosis




1. en.wikipedia.org/wiki/Glycogen_storage_disease_type_1

2. www.ncbi.nlm.nih.gov/entrez/dipomim.cgi/id=232200

3. www.merck.com/mmhe/sec 23/ch 282/ ch 282b

4. pediatrics.aappublications.org/cgi/content/abstract/16/6/785


162

• Learning issues


related to Von Gierke’s disease



session.


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163

Tutorial # 7

Galactosemia

� Introduction During this week you will work through the case of Galactosemia


1. Summarize the metabolic pathway of galactose in the body.

2. Describe the biochemical defect usually found in galactosemia.

3. Predict the biochemical effects of galactosemia.

4. Illustrate the alternate source of galactose.

5. Explain the ability of galactosemic mother to produce lactose in her milk.

6. Interpret the laboratory results obtained from a galactosemic patient.

7. Distinguish the differences if galactosemia is due to galactokinase deficiency.

A boy patient was the first child of healthy parents without known consanguinity.

Delivery was normal and birth weight was 3.78 kg. From the third day of life the child

developed an increasing degree of jaundice and at the same time became indolent and

difficult to feed. No blood group incompatibility could be demonstrated. At 6 days of age

he had a serum bilirubin of 504 µmol/L, and his weight was 15% below normal weight.

Muscular tonus was increased, and the patient later began to convulse. Serum bilirubin

concentration remained high inspite of frequent exchange blood transfusion. On the the

ninth day of life the boy began vomiting, liver enlargement was noted, and the cerebral

symptoms became accentuated.

A positive test for reducing sugars in urine had already been obtained in the sixth day

after birth, which also obtained on the seventh day, while a test for glucose in urine was

negative. Hereditary galactosemia was then suspected, and special tests that were

performed on the eighth day of life confirmed the diagnosis:

Hemoglobin 12.4 mmol/L (200 g/L)

AST 299 U/L

ALT 202 U/L (normal after seventh day)

Bilirubin (max) 549 µmol/L (at seventh day)

Glalactose-1-P uridyl transferase 0 (normal 2 – 31 units/g of hemoglobin)

(in erythrocytes)

Milk feeding was stopped on the ninth day, and it was replaced by intravenous glucose

administration. From the tenth day of life, galactose-free diet was introduced. With this

treatment the patient improved dramatically.


164

1. Illustrate the pathway for galactose metabolism

2. What is the biochemical defect in classic galactosemia?

3. What are the biochemical effects of galactosemia?

4. Is there an alternate source of tissue galactose for patient on a galactose-free

diet?

5. Would a homozygous galactosemic mother be able to produce lactose in her

milk ?

6. How would a D-galactose tolerance curve have appeared if it had

(unfortunately) been given to the patient?

7. What are the interpretations of the laboratory results?

8. What differences would have been noted if the deficient enzyme had been

galactokinase

1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey P: 107 - 114



1. www.savebabies.org/diseasedescriptions/galactosemia.php

2. www.nlm.nih.gov/medlineplus/ency/article/000366.htm

3.www.wikipedia.org/wiki/galactosemia

4.www.nvbi.nlm.nih.gov/entrez/dispomim.cgi/id=230400

5.www.merck.com/mmpe/sec19/ch296/ch296d.html

6. children.webmd.com/Galactosemia-Test


165

• Learning issues


related to Galactosemia Try to summarize these learning issues in the table below. We recommend you to


session.


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166

Tutorial # 8

Hereditary Fructose Intolerance

� Introduction During this week you will work through the case of Hereditary Fructose

Intolerance


1. Summarize the metabolic pathway of fructose in the body.

2. Name the enzyme defect in a patient with hereditary fructose intolerance.

3. recognize the biochemical consequences of deficiency of this enzyme.

4. Explain the elevation noted for AST and ALT in fructose tolerance test.

5. Tell why serum concentration of phosphate drops in fructose intolerance.

6. Explain why the symptoms of hypoglycemia are not found in essential

fructosuria.

7. Show the consequences of deficiency of phosphofructokinase in patient with

hereditary fructose intolerance.

8. Discover the manifestations of inhibition of fructokinase enzyme caused by

fructose-1-phosphate in a patient with hereditary fructose intolerance.

A child had nausea, vomiting, and symptoms of hypoglycemia: sweating, dizziness, and

trembling. It was reported that these attacks occurred shortly after eating fruit or cane

sugar. This was resulting in a strong aversion to fruits, and the mother was therefore

providing large supplementations of multivitamin preparations. The child was below

normal weight and was an only child who had been breast fed, during which time none of

these symptoms was evident. The clinical findings included some cirrhosis of the liver, a

normal glucose tolerance test, and reducing substances in the urine that did not react

positively with glucose test papers, in which glucose oxidase was used as the basis for test.

A fructose tolerance test was ordered, using 3 g fructose /m2 of surface, given

intravenously in a single, rapid push. Within 30 minutes the child displayed the symptoms

of hypoglycemia. Blood glucose analysis confirmed this and revealed that the

hypoglycemia was greater after 60 to 90 min. Fructose concentration reached a maximum

after 15 min and gradually decreased to zero in 2 ½ hr. Phosphate concentration fell 50%

and AST and ALT elevation were noted after 1 ½ hr. The urine was positive for fructose.


167

1. Illustrate the metabolic pathway of fructose in the body

2. Explain why the fructose concentration in the blood remained elevated for an

extended period.

3. Explain the elevation noted for AST and ALT in the fructose tolerance test.

4. Why are the symptoms of hypoglycemia not found in essential fructosuria?

5. What would be the consequences of a deficiency of phosphofructokinase in the

patient?




1. www.pennhealth.com/ency/article/000359.htm

2. www.nlm.nih.gov/medlineplus/ency/article/000359

3. ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=229600

4.www.merck.com/mmpe/sec23/ch282/ch282b.html


168

• Learning issues


related to Hereditary Fructose Intolerance



session.


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169

Tutorial # ٩

Hyperlipidemias

� Introduction During this week you will work through the case of Hyperlipidemias


1. Revise cholesterol metabolism & serum lipoproteins metabolism.

2. Be aware of the types of hereditary hyperlipidemias.

3. Recognize why LDL level is increased with familial

hypercholesterolemia.

4. Define the secondary causes of hyperlipidemias

5. Be familiar with the risk factors of coronary artery disease

1. What is the most likely diagnosis?

2. What is the next step after diagnosis?

3. What is the class of medication to be prescribed?

4. What are the possible complications if left untreated?

A healthy 25-year-old man presents for a physical examination and is found to have

markedly elevated total cholesterol (350 mg/dl), LDL cholesterol (266 mg/dl) and

triglycerides (300 mg/dl), and low HDL cholesterol (36 mg/dl). He has an unremarkable

physical examination. He is normotensive, a nonsmoker, but with a strong family history of

hypercholesterolemia and premature atherosclerotic coronary artery disease


170



Try to access CD-ROM series about Hyperlipidemias .

1. http://ull.chemistry.uakron.edu/biochem/18/

2. http://www.dentistry.leeds.ac.uk/biochem/thcme/lipoproteins.html

3. http://www.biocarta.com/pathfiles/h_LDLPathway.asp

4. 4- nfs.uvm.edu/nfs-new/activities/tutorials/lipid.html


171

• Learning issues


related to Hyperlipidemias



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Tutorial # 10

Gallstones

� Introduction During this week you will work through the case of Gallstones


1. Be familiar with bile salt metabolism and regulation

2. Be able to identify where bile salts are synthesized.

3. Define where bile salts emulsify dietary fats.

4. Differentiate between the types of gallstones

5. Be familiar with the clinical picture, complications & treatment of

gallstones

6. Recognize the pathogenetic mechanism of gallstone formation

1. What are gall stones made of?

2. Can gall stones be seen on abdominal X-ray

3. What are the factors needed to consider performing cholecystectomy?

A 45-year-old female presents with midepigastric pain and nausea/vomiting after eating

fatty meals. She had been told that she had elevated cholesterol levels, her physical

examination is completely normal, but an abdominal ultrasound show few gallstones in the

gall bladder


173



Try to access CD-ROM series about Gallstones

1.http://ull.chemistry.uakron.edu/biochem/18/

2.http://www.uic.edu/depts/mcam/mcbc/handouts/lect26.pdf

3.http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm

4.http://www.dentistry.leeds.ac.uk/biochem/thcme/cholesterol.html

5. http://www.biocarta.com/pathfiles/h_s1pPathway.asp


174

• Learning issues


related to Gallstones



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€¦ · · 2010-05-05clinical study in stage iii of the mbbs program. ... the aim of clinical...

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