b.sc. biochemistry sem 1 introduction to biochemistry unit 4 metabolism and bioenergetics

Course: B.Sc. Biochemistry

Sub: introduction to biochemistry

Unit -4

Metabolic Concepts Metabolism, the sum of all the chemical transformations

taking place in a cell or organism, occurs through a series of enzyme-catalyzed reactions that constitute metabolic pathways.

Each of the consecutive steps in a metabolic pathway brings about a specific, small chemical change, usually the removal, transfer, or addition of a particular atom or functional group.

The precursor is converted into a product through a series of metabolic intermediates called metabolites.

The term intermediary metabolism is often applied to the combined activities of all the metabolic pathways that interconvert precursors, metabolites, and products of low molecular weight (generally, Mr 1,000).

Catabolism is the degradative phase of metabolism in which organic nutrient molecules (carbohydrates, fats, and proteins) are converted into smaller, simpler end products (such as lactic acid, CO2, NH3).

Catabolic pathways release energy, some of which is conserved in the formation of ATP and reduced electron carriers (NADH, NADPH, and FADH2); the rest is lost as heat.

In anabolism, also called biosynthesis, small, simple precursors are built up into larger and more complex

molecules, including lipids, polysaccharides, proteins,

and nucleic acids.

Anabolic reactions require an input of energy, generally in the form of the phosphoryl group transfer potential of ATP and the reducing power of

NADH, NADPH, and FADH2 (Fig. 3).

Some metabolic pathways are linear, and some are branched, yielding multiple useful end products from a single precursor or converting several starting materials into a single product. In general, catabolic pathways are convergent and anabolic pathways divergent .

Some pathways are cyclic: one starting component of the pathway is regenerated in a series of reactions that converts another starting component into a product.

Three types of nonlinear metabolic pathways. (a) Converging, catabolic; (b) diverging, anabolic; and (c) cyclic, in which one of the starting materials (oxaloacetate in this case) is regenerated and reenters the pathway. Acetate, a key metabolic intermediate, is the breakdown product of a variety of fuels (a), serves as the precursor for an array of products (b), and is consumed in the catabolic pathway known as the citric acid cycle (c).

Bioenergetics Life is an energy intensive

process.

It takes energy to operate muscles, extract wastes, make new cells, heal wounds, even to think.

BioenergeticsA discipline within

biochemistry dedicated to the study of energy flow within living systems

Why Study Bioenergetics?

The understanding of metabolism provides the directions to better understand how skeletal muscles generate energy, and how and why the body responds to exercise the way it does.

The study of metabolism is aided by studying Bioenergetics.

The Laws of Bioenergetics provide the rules upon which metabolism functions.

Thermodynamics The study of energy transformations that occur in a

collection of matter.

Two Laws:

1. First Law of Thermodynamics

2. Second Law of Thermodynamics

First Law of Thermodynamics

Energy cannot be created or destroyed, but only converted to other forms.

This means that the amount of energyin the universe is constant.

The First Law is not much help...What prevents a melting ice cube from

spontaneously refreezing?

Why doesn’t water flow uphill?

Will L-alanine convert into D-alanine?

The energy of the system and its surrounds won’t

change.

If it does not occur, what is driving force?

What can we learn from the 1st law of bioenergetics

1. The main forms of energy within the body are;

• heat light mechanical

• chemical

• “free energy”

• entropy

2. Entropy is a form of energy that cannot be re-used in chemicalreactions, and is defined synonomously with increasedrandomness or disorder.

3. “Free energy” is referred to as Gibb’s free energy, and isabbreviated “G”. Typically, during energy transfers there is achange in energy forms, which is indicated by the “∆“ symbol.Thus, a change in Gibb’s free energy is expressed as a “∆G”.

The Second Law helps resolve problem

Only those events that result in a net increase in disorder will occur

spontaneously

Second Law of Thermodynamics

All energy transformations are inefficient because every reaction results in an increase in entropy and the loss of usable energy as heat.

Entropy: the amount of disorder in a system.

Second law: The second law of thermodynamics, which can be

stated in several forms, says that the universe always tends toward increasing disorder: in all natural processes, the entropy of the universe increases.

Living organisms consist of collections of molecules much more highly organized than the surrounding materials from which they are constructed, and organisms maintain and produce order, seemingly oblivious to the second law of thermodynamics. But living organisms do not violate the second law; they operate strictly within it.

Lessons learnt from the 2nd law of bioenergetics

1. All reactions proceed in the direction of:

a) ↑ entropy

b) a release of free energy (-∆G,(Kcal/Mol))

2. The more negative the ∆G, the greater the release of freeenergy during a chemical reaction.

3. Chemical reactions that have a -∆G are termed exergonicreactions.

4. By convention, reactions that require free energy input toproceed are termed endergonic reactions, but there are nosuch reactions in the human body!

5. The free energy not used to do work is expressed as heat.

6. Reactions that have no net change in substrate or product are termed equilibrium reactions, and have no change in free energy (∆G=0).

7. All reactions are potentially reversible.

8. The directionality and amount of free energy release of a chemical reaction can be modified by altering substrate and product concentrations.

- ↑’ing products may reverse the direction of the reaction

- ↑’ing substrates can make the ∆G more negative

Of course, if the reaction is reversed, what were the

products are now the substrates, and vice-versa

The second Law; The entropy (disorder) of the universe is increasing

3

Mitochondria:

1

STATE STANDARD:

“Students know that in both plants and animals,

mitochondria make stored chemical bond

energy available to cells by completing the

breakdown of glucose to carbon dioxide!”

Mitochondria:

1

• have complex folded inner membranes (cristae), increasing their surface area

Mitochondria:


• have a fluid-filled interior (the matrix)

Mitochondria:


• have a fluid-filled interior (the matrix)

• act like combustion chambers in an engine,a ‘safe’ place to ‘burn’ fuel with oxygen

Mitochondria:

A Combustion Chamber?

A Combustion Chamber?LET’S COMPARE!

A gasoline engine . . . . and a mitochondria,in cross-section.

2

Before combustion canoccur, however, we have to

get some “fuel” !

For that, we will need to break down glucose(or other sugars) OUTSIDE

the mitochondria, in a process called . . . .

is the breakdown of glucose (orother sugars)


requires an activation energy


requires an activation energy

occurs in the cytoplasm

Polymers of glucose, like starch, are first broken into individual sugars through

hydrolysis

The single sugars produced containstored energy in their chemical bonds,

but they are still too big to pass through the mitochondrial membrane.

ATP provides the initial activation energy. The 6-carbon sugar willbe broken down in a series of steps

that do not involve oxygen.

There will be a net gain of 2 ATP. The final products of glycolysis are two 3-carbon molecules of pyruvate (pyruvic

acid)

C3H3O3

3

Pyruvate is small enough tobe easily transported through the mitochondrial

membrane, where a new series of chemical reactionstake place. . .

C3H3O3

TheKrebsCycle

The Krebs Cycle:

• takes place in the matrix

4

The Krebs Cycle:

• takes place in the matrix

• begins by converting each of the 3-carbonpyruvates into a special complex calledacetyl CoA

C3H3O3 “acetyl CoA”

. . Co-enzyme A is added

Pyruvate entersthe matrix. . . . . .a waste product ,

CO2 , is released . . .

The Krebs Cycle:Acetyl CoA

begins the cycleAcetyl CoA

The Krebs Cycle:Acetyl CoA

begins the cycle

As the cycle proceeds, CO2

are removed

CO2

CO2

The Krebs Cycle:There is a netgain in ATP,

and . . .

. . .an electron transport chain

is charged!

ATP

CO2

CO2e-

e-

Electron Transport:

• takes place in the cristae

Electron Transport:

• takes place in the cristae

• will draw in H+, creating a highconcentration which can be used to

drive a proton pump

Electron Transport:

Proton Pumping:

• powers the enzyme, ATP synthase

Proton Pumping:

• powers the enzyme, ATP synthase

…which is then used to make ATP

DOING THE MATH:

Glycolysis, in cytoplasm, no O2 4 ATP

DOING THE MATH:


Krebs Cycle, in matrix, no O2 2 ATP

DOING THE MATH:



Electron transport chains, with O2 32 ATP

DOING THE MATH:




TOTAL: 38 ATP

DOING THE MATH:

Glycolysis, in cytoplasm, no O2 4 ATP*



TOTAL: 38 ATP(-2 ATP)*---------------

(*minus 2 ATP used for activation energy in glycolysis)

DOING THE MATH:

Glycolysis, in cytoplasm, no O2 4 ATP*



TOTAL: 38 ATP(-2 ATP)*---------------

NET YIELD, 1 glucose: 36 net ATP

(*minus 2 ATP used for activation energy in glycolysis)

MINERALS A mineral is a naturally occurring substance that is

solid and stable at room temperature, representable by a chemical formula, usually abiogenic, and has an ordered atomic structure. It is different from a rock, which can be an aggregate of minerals or non-minerals and does not have a specific chemical composition. The exact definition of a mineral is under debate, especially with respect to the requirement a valid species be abiogenic, and to a lesser extent with regard to it having an ordered atomic structure. The study of minerals is called mineralogy.

Functions of Minerals Some participate with enzymes in metabolic

processes (cofactors, e.g. Mg, Mn, Cu, Zn, K)

Some have structural functions (Ca, P in bone; S in keratin)

Acid-base and water balance (Na, K, Cl)

Nerve & muscle function (Ca, Na, K)

Unique functions: hemoglobin (Fe), Vitamin B12

(Co), thyroxine (I).

Classification

Macro or Major minerals

Sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), phosphorus (P), sulfur (S), chloride (Cl)

Present in body tissues at concentrations >50 mg/kg

requirement of these is >100 mg/d

Micro or Trace minerals(body needs relatively less) Manganese(Mg), iron(Fe),

cobalt(Co), chromium(Cr),molybdenum(Mo), copper(Cu), zinc(Zn), fluoride(F), iodine(I), selenium(Se)

Present in body tissues at concentrations <50 mg/kg

requirement of these is ﹤100 mg/d

Nutritionally Important Minerals

Macro Trace

Element g/kg Element mg/kg

Ca

P

K

Na

Cl

S

Mg

15

10

2

1.6

1.1

1.5

0.4

Fe

Zn

Cu

Mo

Se

I

Mn

Co

20-50

10-50

1-5

1-4

1-2

0.3-0.6

0.2-0.5

0.02-0.1

Minerals in Foods Found in all food groups.

More reliably found in animal products.

Often other substances in foods decrease absorption(bioavailability) of minerals Oxalate, found in spinach, prevents

absorption of most calcium in spinach.

Phytate, form of phosphorous in most plants makes it poorly available

Oxalate

Phytate

Factors Affecting Requirements

Physiological state/level of production

Interactions with other minerals

4

Deficiencies and Excesses Most minerals have an optimal range

Below leads to deficiency symptoms

Above leads to toxicity symptoms

Mineral content of soils dictates mineral status of

plants (i.e., feeds)

May take many months to develop

Requirements and Toxicities

Element Species Requirement, mg/kg

Toxic level, mg/kg

Cu Cattle

Swine

5-8

6

115

250

Co Cattle 0.06 60

I Livestock 0.1 ?

Se Cattle

Horses

0.1

0.1

3-4

5-40

Calcium (Ca)

Most abundant mineral in animal tissues 99% Ca in skeleton 1% Present in:

Blood & other tissues

Lots of functions Bone structure Nerve function Blood clotting Muscle contraction Cellular metabolism

5

Dietary requirements

Dietary requirements:

Adult : 800 mg/day;

Women during pregnancy, lactation and post-

menopause: 1.5 g/day;

Children (1-18 yrs): 0.8-1.2 g/ day;

Infants: (< 1 year): 300-500 mg /day

Food Sources:

Best sources: milk and milk product;

Good sources: beans, leafy vegetables, fish, cabbage, egg

yolk.

Major minerals

Sodium-sources- table salt, processed foods-metabolism- water balance

-acid base balance (excretion ofhydrogen ions in exchange for sodium ions in kidney)

Major minerals

Chloride-sources- table salt, processed foods-metabolism- water balance

-hydrochloric acid

Major minerals

Potassium--sources-all whole foods, meats, milk,

fruits, grains

-metabolism- water balance-supports cell integrity-promotes steady heartbeat

Major minerals

Calcium

-sources-milk and milk products, small fish with bones, tofu, broccoli, chard

-metabolism- bone and teeth formation

-cell signalling

Major minerals

Phosphorous-sources-all animal tissues

-metabolism- buffers-part of DNA/RNA-phosphorylation of many

enzymes and B vitamins to make them biochemically active

-ATP-phospholipids-cell signalling

Major minerals

Magnesium

-sources-nuts, legumes, whole grains, dark green vegetables,

seafood, chocolate

-metabolism- enzyme co-factor (glucose use in body plus

synthesis of protein, lipids and nucleic acids)

-part of enzyme that transforms ADP to ATP

Major minerals

Sulphur-sources-all protein containing foods

-metabolism- protein structure-part of thiamine and

biotin

Minor minerals

Definition of minor minerals

-present in body in amounts less than 5 grams

Minor minerals

Inorganic elements

•Iron

•Zinc

•Iodine

•Selenium

•Copper

•Manganese

•Fluoride

•Chromium

• Molybdenum

Minor minerals

Body's handling of minerals

-iron uses carriers for absorption, transport and proteins for storage-no free iron- oxidation issue-example of minor mineral requiring no carriers or storage proteins iodine

Variable Bioavailability-phytates reduce iron absorption

Minor minerals

Nutrient Interactions-slight manganese overload may exacerbate iron deficiency

-combined iodine and selenium deficiency reduces thyroid hormone function more than just iodine deficiency alone

Varied roles-iron-oxygen carrying-zinc- part of enzymes

Minor minerals

Iron-sources-red meats, fish, poultry,

shellfish, eggs, legumes, dried fruits

-metabolism- oxygen carrier-part of electron carriers

in electron transport chain

Minor mineralsZinc

-sources-protein containing foods:meats fish, poultry, whole grains, vegetables

-metabolism- part of many enzymes-synthesis of DNA/RNA-heme synthesis-fatty acid metabolism-release hepatic stores of

vitamin A-carbohydrate metabolism-synthesis of proteins-dispose of damaging free radicals

-oxygen carrying

Minor minerals

Iodine-sources-iodised salt, seafood, bread,

dairy products, plants grown on iodine rich soil and animals that eat such plants

-metabolism- thyroid hormones-metabolic rate(rate of oxygen use),body temperature

Minor minerals

Selenium-sources-seafood, meat, whole grains, and

depending on soil selenium content- vegetables

-metabolism- anti-oxidation (via enzyme)- regulates thyroid hormone

Minor mineralsCopper

-sources-seafood, nuts, whole grains, seeds, legumes

-metabolism- part of many enzymes all of which have common feature of

consuming oxygen or oxygen radicals-eg -hemoglobisynthesis

-collagen synthesis-free radical control-electron transport

chain

Minor minerals

Manganese-sources-nuts, whole grains, leafy

vegetables

-metabolism- essential for iron absorption and use in formation of hemoglobin -part of several enzymes

Minor minerals

Fluoride

-sources-fluoridated drinking water, tea, seafood

-metabolism- formation of bones and teeth, resistance to tooth decay

Minor minerals

Chromium-sources-meat, unrefined foods, fats,

vegetable oils

-metabolism- enhancing insulin activity

Minor minerals

Molybdenum-sources-legumes, cereals, organ meats

-metabolism- co-factor for several enzymes

References/Sources All images are from Lehninger Principles of biochemistry by Nelson and Cox except1.https://lh4.ggpht.com/0HlIrSFqDcCtidmS1T6x70CquY2CThQM6i_eY3ZuxEt4lC0_yLvjFTwsBiuS6isLH

Azb=s1232.https://lh4.ggpht.com/J4qU9fcv42V2pQj7Wt99lTqMZQZedjEaafMd4CahkTo9euleEuWRbjwSTcnDK1

VIzPbTLg=s933. https://lh5.ggpht.com/CYhZcxlIn01H7O77jW4gz-

6MPxYJ59IzvMJbV6utSh2FX0505P7Ab1fLHQcFE2Zxbv-JBVk=s854.https://lh3.ggpht.com/cc8HBCMzPlDFxXgQKwjk9ZYkOJLotGmbUa4ZzwusqvslbQY7W2UVhXUgVd_

Oj8YGtK6wWw=s1395.

https://lh3.ggpht.com/cHAfbDE2a1aKZfi_VuC9uzkrvK2YjakVMmONrNPcchJcwcsOaYYgOk4wXL_YzeX0E15iEw=s97

6.https://lh3.ggpht.com/eWm_hMna_I6Wapkaq33984aHnCZk8cjgh354pbqKU1BNtZ9kAcNNnaEwGVUZT5FtwR27eow=s85

Books/ Web resources Lehninger Principles of biochemistry by Nelson and Cox www.nlm.nih.gov/medlineplus/minerals.html https://chemistry.osu.edu/~woodward/ch121/ch5_law.htm biochem.co/2010/02/glycolysis www.elmhurst.edu/~chm/onlcourse/CHM103/Rx24citricacidcycle

b.sc. biochemistry sem 1 introduction to biochemistry unit 4 metabolism and bioenergetics

Education

study of metabolism

bioenergetics metabolism

metabolic conceptsmetabolism

study of energy flow

anabolic pathways divergent

input of energy

metabolism functions

understanding of metabolism