mid term #1 study guide 1 lecture 1 what is science empirical science –observational, descriptive...
TRANSCRIPT
Mid Term #1
Study Guide 1
Lecture 1 What is Science• Empirical Science
– Observational, descriptive Science
– Detecting patterns, or departures from patterns
• Theoretical Science– Generating and testing models
(hypothesis testing)– Concerned with explaining
observations and making predictions
• Technological Science– Generating new methods and
processes– Troubleshooting
Basic Assumptions/ Beliefs• Materialism and Naturalism
1. Operate in a closed system2. Nothing interferes with the
system3. All events are totally
dependent on the whole system
4. Natural explanation for all phenomena
• Scientific Knowledge is based on methodology– Observation– Hypothesis– Experimentation– Dynamic, not static
Scientific ReasoningScientific Reasoning(Propositional Logic)(Propositional Logic)
Inductive Logic• Reasoning from Experiences• Knowledge Expanding
– Contains more information than premise
Deductive Logic• Start with general knowledge
and predict a specific observation
• Truth preserving– Contains less information than
premises
Key Terms• Postulate• Premise• Principle• Theory• Hypothesis• Test
• Principles of Inductivism • The number of
observations forming the basis of a generalization must be large
• Observations must be repeated under a variety of conditions
• No observations should conflict with universal laws, principles, or theories
Problems with Inductivism• Appeals to logic• Appeals to experience• How many observations are
required?• What constitutes significant
variation• Must retreat to probability• Theory: dependent on inductivism• Inductivism fails to throw new light
on science
Recognize an example of inductive reasoning
DeductionProcessProcess
1.1. Statement of problemStatement of problem
2.2. Hypothesis as to the Hypothesis as to the cause of the problemcause of the problem
3.3. Experimental tests for Experimental tests for each hypothesiseach hypothesis
4.4. Predict results (how to Predict results (how to accept or reject the accept or reject the hypothesishypothesis
5.5. Observe resultsObserve results
6.6. Draw conclusions from Draw conclusions from the results (accept or the results (accept or reject the hypothesis)reject the hypothesis)
Premis•Fundamental Assumptions•Must be both valid and true
Good tests •Prediction is logically deducible•Prediction is improbable•Prediction is verifiable
Deductive Process
Problem
Hypothesis
Test
Prediction
Observation
Conclusion
Class is too large
If I make this confusing, then some students will drop
Deliver miserableLecture about logic
Some people will get confused and drop
Acc
ept
Rej
ect
Observation?
No DropsNo Drops Loads-O-DropsLoads-O-Drops
RejectReject AcceptAccept
Was This a Good Example?Was This a Good Example?
DeductionDeduction
Premis, Fundamental Assumptions
Must be both valid and true
Good tests
Prediction is logically deducible
Prediction is improbable
Prediction is verifiable
Facts Facts acquired acquired through through
observationobservation
Laws and Laws and theoriestheories
Predictions Predictions and and
explanationsexplanations
InductionInduction DeductionDeduction
Hypothetico-Deductive MethodHypothetico-Deductive Method
Deductive FalsificationDeductive Falsification(Conjectures and Refutations)(Conjectures and Refutations)
• Positivist- – Only has supporting
evidence– Ignores evidence
against
The Process of Popperian The Process of Popperian FalsificationFalsification
Falsification science: •The process of developing a set of hypotheses, tentatively proposed, to as accurately as possible describe an aspect of the natural world.
Hypotheses must be falsifiable: •One develops logically possible observations which, if established, would falsify the H0.
Problems with Falsification:• Complexity of any realistic test of most modern theories is often extremely difficult.•Theory underlying hypotesis may be false.•The premise behind hypothesis is false.
Example of Falsification from Induction•Many lectures on the philosophy of science are boringMany lectures on the philosophy of science are boring•This is a lecture on the philosophy of scienceThis is a lecture on the philosophy of science•Therefore, this class is boringTherefore, this class is boring
What is the experiment that would falsify or disprove our hypothesis?What is the experiment that would falsify or disprove our hypothesis?
Objectivism vs. SubjectivismObjectivism vs. Subjectivism
Role of the ScientistUnderstanding whether science and scientists are objective or subjective is important in understanding what science is. These are not models but definitions of how science is practiced.Science ValuesScience ValuesScientific Knowledge is not good or bad…Its Goodness or Badness depends on how it’s used and by what standard you grade it.
Is science and are scientists objective? •Subjectivism holds that man is not objective, but subjected to his surroundings, training, personal experience, etc.•Objectivism is the belief that mankind can be removed from or independent of his surroundings and experiences while making observations.
Objectivism and Subjectivism result in at Objectivism and Subjectivism result in at least three concurrent views of scienceleast three concurrent views of science
•2- 2- Postmodern Postmodern RelativismRelativism •Plurality of TruthsPlurality of Truths
Science is only one form Science is only one form ofof Subjective Truth Subjective Truth•Science has made Science has made errors in the past, errors in the past,
Therefore, science Therefore, science and scientists and scientists should be:should be:
•Questioned, Questioned, Evaluated and Evaluated and RegulatedRegulated
SubjectivismSubjectivism holds that science holds that science and scientists are not objective, and scientists are not objective, but antecedents to surroundings, but antecedents to surroundings, training, personal experience, training, personal experience, etc.etc.
1- Scientific 1- Scientific ImperialismImperialism •Science is the Truth Science is the Truth ArbiterArbiter
•Therefore, Therefore, anything goes if anything goes if scientists say soscientists say so
Objectivism is the belief that a scientist can be removed from or independent of his surroundings and experiences while making observations, conclusions and recommendations.
3- Godisms3- GodismsMankind is created and ultimately Truth is God Revealed.
Science is a product of mankind, therefore science must be carefully evaluated for its potential good and/or bad outcomes.
Since truth is ultimately Revealed and science is error prone, science is subjective and an ethical society must take care to evaluate and judge science’s pursuits and products carefully.
Science: Research programs• Hard core theory, often not
easily challenged• Generates lots of Hypotheses
Problems: 1) Politically influenced, 2) Special interest influenced, 3) Dictate large expenditures of public funds, 4) Redirect or sometimes misdirect science thrusts and 5) Often ideologically driven or oriented.
Examples: Genomics, NASA, Aids Research, Cancer Research, Human Genome Project, etc.
Progress
Degenerate
Kuhn’s Scientific Revolution
Prescience
Crisis
Normal Science
Revolution
A Scientific Theory is likea pitcher of water.
When one Theory fails its components often flow into
another Theory.
Scientific knowledge is dynamic and changeswith new discoveries and additions of newinformation
Lecture 1: What is Science wrap-upLecture 1: What is Science wrap-up
• Human endeavor dependent on the scientific community and societyand society.
• Not infallible, often guided by scientific fads, yet the best we have.we have.
• There are at least 4 ways of describing Science: Inductivism, Falsification, Science Programs & Kuhnian Revolutions.
• Based on presuppositions about how the world is, & many if not all, of these presuppositions are not scientifically testable.
LectureLecture 2: Outline 2: Outline• What is life
– Characteristics- Definition- – Properties- Dynamic changing– Components- building blocks– Minimal life- simplest life forms
• Organizing Life– Taxonomy
• Functions of Life– Metabolism
• Plant• Animal• Carbon, nitrogen and water cycling
• Origin of Life– Where did it come from
• Current Models
• Introduction to Biological Chemistry
What Is Life
Properties of LifeProperties of Life • Dynamic = changing Dynamic = changing • Adaptability • Contain Information (DNA)Contain Information (DNA)• Ordered StructureOrdered Structure• Uniformity of classDefinition of LifeDefinition of Life• An organismic state characterized by the An organismic state characterized by the
capacity for metabolism, growth, reaction to capacity for metabolism, growth, reaction to stimuli, and reproduction.stimuli, and reproduction.
• A principle or force that underlies the A principle or force that underlies the distinctive quality of animate beings.distinctive quality of animate beings.
• The quality that distinguishes a vital and The quality that distinguishes a vital and functional organism from inanimate objects.functional organism from inanimate objects.
Characteristics of DeathCharacteristics of Death• Absence of life• Total and permanent cessation of all vital Total and permanent cessation of all vital
(living) function(living) function• Absence of the characteristics of lifeAbsence of the characteristics of life
Key Terms in “Life” DefinitionKey Terms in “Life” Definition• MetabolismMetabolism
– Acquires and expends “energy”Acquires and expends “energy”• GrowthGrowth
– Makes what it needsMakes what it needs• Reaction Reaction
– Senses EnvironmentSenses Environment• ReproductionReproduction
– A population of one and only one is going to run A population of one and only one is going to run into trouble sooner than laterinto trouble sooner than later
Smallest Components of Life• Elements (atoms)Elements (atoms)• Molecules Molecules • MacromoleculesMacromolecules
– Information carriersInformation carriers• Enzymes, proteinsEnzymes, proteins
– Functional capacityFunctional capacity• Membranes and wallsMembranes and walls
– Boundaries, and containersBoundaries, and containers
Categories of life’s Categories of life’s componentscomponents
Atoms, Amino Acids, Macromolecules, Organelles, Cells, Cells, Organ, Systems, Symbiotic organisms, Individual, Populations
Life QuantitativelyLife QuantitativelyComplexity
– High– Low
Assignment: Learn the metric measuring system and life sizes
How Biologists Measure Size: MetricsHow Biologists Measure Size: Metrics
How simple can life be?How simple can life be?
HIV
Phytoplasma and MycoplasmaPhytoplasma and Mycoplasma = = simplest cellsimplest cell, lack a cell wall, , lack a cell wall, DNA for 200 functions (walking pneumonia, STD’s)DNA for 200 functions (walking pneumonia, STD’s)
Not CellsNot Cells
•Virus = RNA or DNA wrapped in protein coat (HIV, poliomyellitis)
• Viroid = Tightly wound DNA or RNA (coconut cadang cadang, bunchy top)• Prions = 1/100 to 1/1000 the size of a virus, composed of proteins (Scapies, Multiple Sclerosis, Lou Gehrig’s disease)
Pneumonia mycoplasmaPneumonia mycoplasma
Is each of these really alive?
Are they independent?
Can they reproduce or metabolize on their own?
Organizing LifeOrganizing LifeSystematicsSystematicsTaxonomyTaxonomyCladisticsCladisticsPhylogenicsPhylogenics
• Methods of ClassificationMethods of Classification– Based on some relevant Based on some relevant
distinguishing characteristicdistinguishing characteristic– It should be meaningfulIt should be meaningful– It should not be arbitraryIt should not be arbitrary
• Basis of ClassificationsBasis of Classifications– Morphological characteristicsMorphological characteristics
• Types of structures, Types of structures, Size, Diet, ReproductionSize, Diet, Reproduction
– Molecular characteristicsMolecular characteristics• Mitochondrial DNAMitochondrial DNA• Nuclear DNANuclear DNA
ClassificationClassification• Kingdom• Phylum• Class• Order• Family• Genus• Species
ClassificationClassificationThe KingdomsThe Kingdoms• Animalia- multicelluar, consumersAnimalia- multicelluar, consumers• Plantae- multicellular, producersPlantae- multicellular, producers• Fungi- mostly decomposersFungi- mostly decomposers• Protista- One-celled, producers and consumersProtista- One-celled, producers and consumers• Eubacteria- Normal, true bacteria, consumers…Eubacteria- Normal, true bacteria, consumers…• Archaebacteria- Extreme bacteria, consumers…Archaebacteria- Extreme bacteria, consumers…
Basic Premis (assumption) of taxonomy “Natura non facit saltum” (Nature does not make leaps).
So Who’s RelatedSo Who’s RelatedDNA sequences provide a direct record of the genealogy of extant species. surprising changes have recently been proposed for The tree of mammalian orders. These range from grouping whales with hippos, to placing African golden moles closer to elephants than to their fellow insectivores.Molecules remodel the mammalian tree Wilfried W. de JongTrends in Ecology & Evolution 1998, 13:270-275
Classification schemes generate different trees based on which sorting criteria is used.
Trees based on physical characteristics or reproductive characteristics are often different from trees made from comparisons of DNA. The specific DNA used also generates different trees. Mitochondrial DNA, or different nuclear genes encoding common proteins can each generate different trees.
Functions of LifeFunctions of Life Four categories for organizing the characteristic of life: Four categories for organizing the characteristic of life:
Metabolism, Growth, Reaction, ReproductionMetabolism, Growth, Reaction, Reproduction
MetabolismMetabolism• Storing and releasing energyStoring and releasing energy• Converting light energy into Converting light energy into chemical energychemical energy
• Plants fix carbon from the airPlants fix carbon from the air• Animals release carbon from Animals release carbon from storage molecluesstorage moleclues
GrowthGrowth•Using the stored energy•Incorporating acquired materialsCatabolic processes- breaking downAnabolic processes- building up
Reaction• Sensing environment
– Receptors andMetabolic changes
• Reacting to changing environmentExamples from Bacteria, Plants
and Animals• Reacting to internal environment:
HomeostasisReproductionReproduction• Sexual Reproduction: Cell
Process: Meiosis and Mixing Genes
• Replication, Division: Cell Process: Mitosis and High fidelity copies
• Adaptation and Selection
Where does life come from?Objectivism and Subjectivism result in different views of science. These views and their assumptions affect fundamental questions of science
Three Models • Neo-Darwinian
– Macro Evolutionary Process• Cosmic Inoculation
– Panspermia• Divine Creation
The Standard StoryThe Big Bang
• 12-15 billion years ago all matter was
compressed into a space the size of our sun
• Sudden instantaneous distribution of matter and energy throughout the known universe
• Planet Formation– About 4.6 and 4.5 billion years ago
• The Earth formed and conditions were just right
• The right kinds of molecules formed• The right molecules assembled
Is Life is a property of matter and energy?
Abiogenesis Origin (Neo-Darwinian)Macro Evolutionary ProcessChance, Necessity, and Self OrganizationChemical processes generated life precursorsPrecursors assembled into proto cells
Extraterrestrial deposition (Panspermia)Organisms came from somewhere elseChemistry came from somewhere else
PresuppositionsPresuppositionsDo Presuppositions Matter?
– Naturalism and Materialism– Life is a property of matter and energy– Chance, Necessity, and Self Organization
• Of course it works, we’re here aren’t we?
Origin of LifeOrigin of Life Where did it come from?Where did it come from?
New ideas, new questionsNew ideas, new questionsMatter, Energy, and InformationWhere does the information come from?
Identifying LifeDoes Life Exist Elsewhere in the Universe?
• Are terrestrial biochemistry and molecular biology the only such phenomena that can support life?
• With only one example, we don’t know which properties of life are general and necessary, and which are the result of specific circumstances or historical accident.
Prescience
Crisis
Normal Science
Revolution
Its life Jim, but not as we know it
SummarySummaryDefinitions PropertiesCharacteristics OrganizationLife and Energy Measuring LifeForms of Simple Life Origin of Life
Lecture 3: Chemistry of Life
Chemical Bonds
ElementsElements• Fundamental forms of matter• Can’t be broken apart by normal meansMost Common Elements in Living Organisms: Oxygen,
Hydrogen, Carbon, and NitrogenWhat Are Atoms?• Smallest particles that retain properties of an element• Made up of subatomic particles:
– Protons (+)– Electrons (-) – Neutrons (no charge)
Atomic NumberAtomic MassAtomic Mass
Isotopes and RadioisotopesIsotopes and RadioisotopesUses of Radioisotopes Uses of Radioisotopes
Tracers, Imaging, Radiation therapyTracers, Imaging, Radiation therapy
HYDROGEN
What Determines Whether What Determines Whether Atoms Will Interact?Atoms Will Interact?
ElectronsElectrons• Carry a negative charge• Repel one another • Are attracted to protons in the
nucleus• Move in orbitals - volumes of
space that surround the nucleus
Electron VacanciesElectron Vacancies• Unfilled shells make atoms
likely to react• Hydrogen, carbon, oxygen,
and nitrogen all have vacancies in their outer shells
Chemical Bonds, Molecules, Chemical Bonds, Molecules, & Compounds& Compounds
• Bond is union between electron structures of atoms
• Atoms bond to form molecules• Molecules may contain atoms
of only one element - O2
• Molecules of compounds contain more than one element - H2O
Chemical BondsChemical BondsElectrostatic
Covalent
1. Ionic 1. Ionic BondingBonding•One atom loses electrons and becomes a positively charged ion
•Another atom gains an electron and becomes a negatively charged ion
•Charge difference attracts the two ions to each other
Ion FormationIon FormationAtom has equal number of electrons and protons - no net chargeAtom loses electron(s), becomes positively charged ionAtom gains electron(s), becomes negatively charged ion
SODIUMATOM11 p+
11 e-
SODIUMION
11 p+
10 e-
electron transfer
CHLORINEATOM17 p+
17 e-
CHLORINEION
17 p+
18 e-
Chemical BondsChemical Bonds
2. Covalent 2. Covalent BondingBonding •Atoms share a pair or pairs of electrons to fill outermost shell•High energy bonds hold together tightly.•Require high levels of energy to break covalent bonds
Two Flavors of Covalent Bonds
Non-polarNon-polar Covalent Covalent• Atoms share electrons equally• Nuclei of atoms have same number of
protons• Example: Hydrogen gas (H-H)
PolarPolar Covalent Covalent• Number of protons in nuclei of
participating atoms is NOT equal• Molecule held together by polar
covalent bonds has no NET charge• Electrons spend more time near
nucleus with most protons– Example: Water – Electrons more attracted to O nucleus
than to H nuclei
Electrostatic
Covalent
Example
+
O
H H
slight negative charge at this end
slight positive charge at this end
molecule hasno net charge( + and - balanceeach other)
KEEP YOUR EYE ON THE ELECTRONS
Hydrogen BondingHydrogen Bonding
A bond by Hydrogen between two atoms
• Important for O and N
• Lets two electronegative atoms interact– The H gives one a net + and the other one
that is still – is attracted to it.
• The H proton becomes “naked” because its electron gets pulled away.
Hydrogen bond figure
- -
- + -
Like Charge Atoms Repel Each Other
Opposite Charge Atoms Attract Each Other
KEEP YOUR EYE ON THE ELECTRONS
onelargemolecule
anotherlargemolecule
a largemoleculetwistedbackonitself
Hydrogen bonds are the most Hydrogen bonds are the most physiologically relevant chemical bond physiologically relevant chemical bond
in all of nature!!!!in all of nature!!!!
Hydrogen bonds hold DNA strands together and allow them to come apart and reform!
Hydrogen bonds take place between different parts of a polypeptide chain and give the molecule the glue it needs to fold correctly
WaterWaterProperties of WaterProperties of Water• Polarity• Temperature-Stabilizing• Cohesive• Solvent• Molecule has no net chargeWater Is a Polar Water Is a Polar
Covalent MoleculeCovalent Molecule• Oxygen end has a slight
negative charge• Hydrogen end has a slight
positive charge
Hydrophilic & HydrophobicHydrophilic & Hydrophobic• Hydrophilic substances
– Polar– Hydrogen bond with water – Example: sugar
• Hydrophobic substances– Nonpolar– Repelled by water– Example: oil
Water Is a Good SolventWater Is a Good Solvent• Ions and polar molecules dissolve
easily in water • When solute dissolves, water molecules
cluster around its ions or molecules and keep them separated
• Solvent- polar– Keeps ions in solution– Doesn’t dissolve membranes
The pH Scale and pH in generalThe pH Scale and pH in generalMeasures H+ concentration of fluidChange of 1 on scale means 10X
change in H+ concentrationHighest H+ Lowest H+
0---------------------7-------------------14Acidic Neutral Basic
Hydrogen Ions: H+Hydrogen Ions: H+Unbound protonsHave important biological effectsForm when water ionizes
AcidsDonate H+ when dissolved in waterAcidic solutions have pH < 7Strong acids forcefully give up H+
BasesAccept H+ when dissolved in waterAcidic solutions have pH > 7Strong bases forcefully take H+
The problem with water is a static view
H3O+ ↔H2O↔OH-
Draino and battery acid are really bad for your skin. Understanding pH, the basis of protein structure and formation of peptide bonds help you to understand why
Organic CompoundsCarbon’s Bonding Behavior• Outer shell of carbon has 4 electrons; can
hold 8• Each carbon atom can form covalent bonds
with up to four atoms• Carbon atoms can form chains or rings• Other atoms project from the carbon
backboneFunctional Groups• Atoms or clusters of atoms that are
covalently bonded to carbon backbone• Give organic compounds their different
propertiesExamples of Functional GroupsHydroxyl group - OH Amino group - NH3
+
Carboxyl group - COOH-
Phosphate group - PO3-
Sulfhydryl group - SH
Hydrogen and other elements covalently bonded to carbon: Carbohydrates, Lipids, Proteins, Nucleic Acids
Types of ReactionsFunctional group transfer, Electron
transfer, Rearrangement,
Condensation, Cleavage
Condensation Reactions
• Form polymers from subunits
• Enzymes remove -OH from one molecule, H from another, form bond between two molecules
• Discarded atoms can join to form water
Hydrolysis
• A type of cleavage reaction
• Breaks polymers into smaller units
• Enzymes split molecules into two or more parts
• An -OH group and an H atom derived from water are attached at exposed sites
THE MACRO MOLECULESCarbohydrates
Monosaccharides(simple sugars)Oligosaccharides(short-chain carbohydrates)Polysaccharides(complex carbohydrates)Monosaccharides• Simplest carbohydrates• Most are sweet tasting, water soluble• Most have 5- or 6-carbon backbone
Glucose (6 C) Fructose (6 C)Ribose (5 C) Deoxyribose (5 C)
Polysaccharides• Straight or branched chains of many sugar
monomers• Most common are composed entirely of glucose
– Cellulose– Starch (such as amylose)– Glycogen
Cellulose & Starch• Differ in bonding patterns between
monomers• Cellulose - tough, indigestible,
structural material in plants• Starch - easily digested, storage form
in plants
Glycogen • Sugar storage form in animals• Large stores in muscle and liver cells• When blood sugar decreases, liver
cells degrade glycogen, release glucose
Chitin• Polysaccharide • Nitrogen-containing groups attached
to glucose monomers• Structural material for hard parts of
invertebrates, cell walls of many fungi
+ H2O
glucose fructose
sucroseglucose fructose
THE MACRO MOLECULESLipids• Most include fatty acids
– Fats– Phospholipids– Waxes
• Sterols and their derivatives have no fatty acids
• Tend to be insoluble in water
Fatty Acids• Carboxyl group (-COOH) at one end• Carbon backbone (up to 36 C atoms)
– Saturated - Single bonds between carbons
– Unsaturated - One or more double bonds
stearic acid oleic acid linolenic acid
Triglycerides
Fatty acid(s)
Phospholipids
• Main components of cell
membranes
Sterols and Derivatives
• No fatty acids
• Rigid backbone of four
fused-together carbon
rings
• Cholesterol - most
common type in
animals
Waxes
• Long-chain fatty acids linked to
long chain alcohols or carbon rings
• Firm consistency, repel water
• Important in water-proofing
THE MACRO MOLECULESAmino AcidsProperties of Amino Acids• Determined by the “R group”• Amino acids may be:
– Non-polar – Uncharged, polar – Positively charged, polar– Negatively charged, polar
Protein Synthesis• Protein is a chain of amino acids
linked by peptide bonds• Peptide bond
– Type of covalent bond– Links amino group of one amino
acid with carboxyl group of next– Forms through condensation
reaction
Polyamino Acids = polypeptide = protein
THE MACRO MOLECULESProteinProtein Shapes• Fibrous proteins
– Polypeptide chains arranged as strands or sheets
• Globular proteins – Polypeptide chains folded into compact, rounded
shapesProtein StructureProtein Structure• Primary- just the sequence (1D)• Secondary- interactions on the chain (2D)• Tertiary- interactions between parts of the chain
the chain. (3D)• Quaternary- interactions with other chainsPrimary Structure & Protein Shape• Sequence of amino acids• Primary structure influences shape in two main ways:
– Allows hydrogen bonds to form between different amino acids along length of chain
– Puts R groups in positions that allow them to interact
Secondary Structure• Hydrogen bonds form between different parts of
polypeptide chain• These bonds give rise to coiled or extended
pattern• Helix or pleated sheetTertiary Structure • Folding as a result
of interactions between R groups• The 3D structure of a proteinQuaternary Structure • Some proteins are made up of more than one
polypeptide chain• Structure of a protein when it is folded with other
polypeptidesPolypeptides With Attached Organic Compounds• Lipoproteins
– Proteins combined with cholesterol, triglycerides, phospholipids
• Glycoproteins – Proteins combined with oligosaccharides
Examples of Secondary Structure
heme group
coiled and twisted polypeptide chain of one globin molecule
Hemoglobin
DenaturationDenaturation
• Disruption of three-dimensional shape
• Breakage of weak bonds
• Causes of denaturation:– pH
– Temperature
• Destroying protein shape disrupts function
A Permanent WaveA Permanent Wave
hair wrapped around cuticles
differentbridges form
bridgesbroken
hair’scuticle
keratinmacrofibril
one hair cell microfibril (threechains coiled into one strand)
coiled keratinpolypeptidechain
A brief survey of a some protein types
• Structural
• Muscle
• Binding
• Signaling
• Storage protein
• Defensive protein
• Transportation
• Enzymes
StructuralFunction: Hold togetherGive shape
Examples:Hair
Tendons
Ligaments
Structural
Function: Attachment
CollagenA triple helix
Collagenous fiber
Macrofibril
Microfibril
Collagen molecule
Polypeptide chain
Structural Proteins
Crystallins Lens Fibers
Keratin Actin
MuscleFunction: Contraction
Muscle Flagella
Image courtesy of Dr. Fatih Uckun, Parker Hughes Institute, St. Paul, MN
Movement in the CellActin and Myosin VATP Dependent Reaction
Nature Reviews Molecular Cell Biology 2, 387-392 (2001)
Insulin
Function: Messengers
Receptors
Signaling
Function: Store What?
Expensive molecules for later useChemical energy
Ovalbumin- globular glycoprotein
Storage
Protein for Defense• Example: Antibodies
• Key component of immune system
• Label invading microbes as intruders
Function: Moving molecules:
In side the organismBetween cellsInside Cells
Example: Getting O2 to where it’s needed
Hemoglobin: gives blood cells their red color…
Transportation
Concepts in TransportationThe Basic Terms
• Permeability• Diffusion - Gradients• Membrane transport
– Active – Passive– Bulk
Cell Membranes And Selective Permeability
(Think Grapefruit!)
O2, CO2, H2O,and small non-polar molecules
Sugar, and other large,
polar molecules
Iions such as H+, Na+, CI-, Ca++
X
Gradients- Unequal distributionsGradients- Unequal distributionsMembranes are required for gradientsMembranes are required for gradients
Mechanisms ofCrossing Over
(the membrane)
1. Diffusion across lipid bilayer
2. Passive transport
3. Active transport
4. Bulk Transport
Endocytosis
Exocytosis
• Span the lipid bilayer
• Interior is able to open to both sides
• Change shape when they interact with solute
• Play roles in active and passive transport
Transport Proteins
Active Transport
• Movement of target is against the concentration gradient (Think about Water flowing up hill)
• Transport protein requires energy
(Not free, someone pays)
• ATP is often the source of chemical energy
Passive Transport• Going down the gradient
(That whole water runs down hill thing)
• Selective- only some things fit• Not directional- two way door• Its FREE! Does not require
any energy input
Bulk Transport
Exocytosis
Endocytosis
Features of Enzymes
Enzymes make unlikely reactions happen and happen faster
Enzymes aren’t usually reactants or products and usually aren’t used up orseverely altered
The same enzyme usually works for both the forward and reverse reactions
Each type of enzyme recognizes and binds to only certain molecules.(Substrate Specificity)
Enzymes make, break and Enzymes make, break and rearrange chemical bondsrearrange chemical bonds
Activation Energy
• For a reaction to occur, an energy barrier must be surmounted
• Enzymes make the energy barrier smaller
activation energywithout enzyme
activation energywith enzyme
energyreleased
by thereaction
products
starting substance
Induced-Fit Model
two substrate
molecules
active sight
substratescontactingactive siteof enzyme
TRANSITIONSTATE(tightestbinding butleast stable)
endproduct
enzymeunchangedby thereaction
• Substrate molecules are brought together
• Substrates are oriented in ways that favor reaction
• Active sites may promote acid-base reactions
• Active sites may shut out water
Receptor
Inhibitor
Metabolic pathway
Enzyme
Hydrophobic and Hydrophillic
Sterols
Transport protein
Pulling it all together
Why is CholesterolImportant?
Sales of Lipitor grew 25% in 2001 to $4.4 billion. Pfizer
spent $50 million on Lipitor ads last year.
High cholesteroldoesn’t care who
you are
Observational studies provideoverwhelming evidence thatHDL-C is an independent risk
factor for coronary heart disease
Basic Cholesterol Metabolism• We make all the cholesterol we need and it is absolutely
essential• Major sources of circulating cholesterol
– Peripheral cholesterol synthesis– Hepatic cholesterol synthesis– Intestinal cholesterol absorption
• Once synthesized or absorbed it is packaged into lipoprotein complex so that it can be transported
• The problem is getting cholesterol back to the liver– High Density Lipoprotein – Low Density Lipoprotein
• Transport through the cell membrane is receptor mediated
Basic Cholesterol Metabolism• Delivery of cholesterol from other tissues to the
liver results in the formation of Low Density Lipoprotein (LDL) complexes.
• Problem: Big and sticky and form plaques on artery walls– Atherosclerosis- Clogged arteries
• when plaques break loose the plug up arteries
HDL = Good
LDL or VLDL = Bad
Cholesterol and HealthWhat effects your cholesterol level?• Diet
• Exercise
• Genetics
• Age
• Pharmaceuticals
Statins• Originally intended to be antibiotics
– Bacteria need cholesterol too– Found a small molecule in a Penicillum
• Mechanism of Action– Bind a receptor that is just on liver cells– Once inside, get stuck in an enzyme’s active site. Compete
with substrate– HMG-CoA Reductase– Liver cells want more cholesterol to package so they make
more receptors for LDL
• Less synthesis and more adsorption results in lower cholesterol levels.
Statins
What is a good drug anyway?1. Good enzyme inhibitor- a little bit goes a long
way (IC50)
2. Specific tissue action- only works where you want it
3. Pharmacokinetics- goes in fast and stays there a long time.
4. Doesn’t interact with other drugs
Cholesterol Synthesis
Metabolic Pathway• Linear, branched or
cyclic?• What else do we
need HMG-CoA Reductase for?
• Does it only affect liver cells?
Statins on the Market• Atorvastatin, Lipitor, Pfizer• Fluvastatin, Lescol, Novartis• Lovastatin, Mevacor, Merck• Prevastatin, Pravachol, Bristol-Myers
Squibb • Simvastatin, Zocor, Merck• Cerivastatin, Baycol, Bayer
POLAR!
How Good It Works
•The more polar the drug is, the less likely it will be absorbed by non target cells (non-liver)
•More negative side affects are associated with the less polar (more hydrophobic compounds)
Lipophilic=Lipid loving=Hydrophobic
Too Much of a Good Thing
Rhabdomyolysis
•Rapid muscle tissue breakdown. (Quite painful, like a permanent cramp)
•Heme protein-induced renal tubular cytotoxicity, intraluminal cast formation, leading to tubular obstruction (kidney plugs up and you can’t make urine, very bad)
Lecture 3: Chemistry of LifeLecture 3: Chemistry of LifePart 3 of 2Part 3 of 2Goals:• Finish with biochemistry• Understand: 1.)What protein is, 2.)What protein
does, and 3.) how make one• Relate concepts of protein structure and function
to real events and issues
Key Terms: Amino acid, R-group, polypeptide, protein types, Key Terms: Amino acid, R-group, polypeptide, protein types, protein structure, peptide bond, lipoprotein, glycoprotein, protein structure, peptide bond, lipoprotein, glycoprotein,
Assingment:Assingment:For Tuesday, read Ch 12 and 13For Tuesday, read Ch 12 and 13For Thursday, read Ch 8 and 14For Thursday, read Ch 8 and 14
Lecture 5: Nucleic Acids into Protein. (Ch 12 and 13)
Goals– Introduction to nucleic acids, DNA and
replication– Understand how to make a protein
(transcription)
Key Terms: DNA, RNA, nucleic acid, replication, topoisomerase, DNA polymerase, ligase, RNA polymerase, transcription, translation, ribosome, splicing, mRNA, tRNA, initiation, elongation, termination, genetic code, mutations,
virus particle labeled with 35S
virus particle labeled with 32P
bacterial cell (cutaway view)
label outside cell
label inside cell
Hershey Chase Experiment
• Label protein or DNA with radio isotopes
• Infect bacteria with phage particles
• Sheer off the phage (blender)• Separate bacteria and phage
protein• Progeny of the phage
Conclusions:
DNA is the infective material not protein
Strong inference: DNA is genetic information
Viral Infection:
Viral DNA infects bacteria
Viral DNA codes for viral proteins
Viral proteins assemble to form new viral particles
Hershey Chase Expt.
DNA Structure
CovalentBonds
HydrogenBonds
Nucleotide Bases (4)Adenine pairs with ThymineGuanine pairs with Cytosine
Structure and function Relationship•DNA is two nucleotide strands held together by hydrogen bonds•Hydrogen bonds between two strands are easily broken•Each single strand then serves as template for new strand
Making DNA (polymerization) requires energy•Energy for strand assembly is provided by removal of two phosphate groups from free nucleotides. •ATP, CTP, TTP, GTP, all have high energy chemical bonds that can be broken and used to do work. (Reference ATP and chemical energy)DNA Repair•Mistakes can occur during replication•DNA polymerase can read correct sequence from complementary strand and, together with DNA ligase, can repair mistakes in incorrect strand•The other context of repair
–Environmental factors damage DNA too–How is DNA repaired after it has been made?
DNA Replication SummaryEnzymes• Topoisomerase unwinds strands• DNA Polymerase attaches new complementary nucleotides• DNA Ligase connects the bonds between phosphate sugar
backbone of the new nucleotidesChemical Bonds • Break hydrogen bonds with Topoisomerase• Make Hydrogen bonds with DNA Polymerase• Make covalent bonds with DNA LigaseFinal Products• The strand being replicated is the template• Start with one copy of a DNA molecule and end with two copies
– New copies have one new strand and one old strand– Both copies are “identical” to the original
Nucleic Acids Into ProteinsSame two steps produce ALL proteins:1.DNA is transcribed into RNA
–Occurs in the nucleus–Gene promoter is the start stop switch–The promoter determines the start site–RNA is spliced(introns removed, exons kept)–mRNA moves into cytoplasm
2.mRNA is translated into polypeptide chains by ribosomes
–Translation occurs in three steps• Initiation at the start codon• Elongation of the polypeptide chain• Termination at the stop codon
–Proteins are folded polypeptide chains.
Promoter• A base sequence in the DNA that signals where transcription starts
• For transcription to occur, RNA polymerase must first bind to a promoter
• The promoter is the on and off switch for a gene
DNA vs. RNARibonucleic Acid• Bases are G,A,C, & U• Uracil (U) pairs with adenine (A)• Contains 2 ° information• Does other things
Catalytic, Inhibitor…Deoxyribonucleic Acid• Bases are G,A,C, & T• Thymine pairs with adenine• Contains 1° information
Transcription & DNA Replication• Like DNA replication
– Nucleotides added in 5’ to 3’ direction– Unlike DNA replication– Only small stretch is template
• RNA polymerase catalyzes nucleotide addition
• Product is a single strand of RNA
Uricil Base (U) Thymine Base (T)
Sugar is Different
Base PairsAre DifferentDNA RNA
Nucleic Acids Into ProteinsThree Classes of RNAs1.Messenger RNA (mRNA)-Carries protein-
building instruction2.Ribosomal RNA (rRNA)-Major component of
ribosome3.Transfer RNA (tRNA)-Delivers amino acids
to ribosome
Key Players in Translation• Ribosome- Center of action• The tRNAs• Start Codon (Met)• The tRNAs- big cast• The mRNA- translated script• Stop codon
mRNA• Message RNA is a copy of some DNA• The mRNA is used as a template for making
proteins• DNA is never used as a template for
proteins!
Initiation• Initiator tRNA binds to small ribosomal
subunit• Small subunit/tRNA complex attaches to
mRNA and moves along it to an AUG “start” codon
• Large ribosomal subunit joins complexElongation• mRNA passes through ribosomal subunits • tRNAs deliver amino acids to the ribosomal
binding site in the order specified by the mRNA
• Peptide bonds form between the amino acids and the polypeptide chain grows
Termination• A stop codon in the mRNA moves onto the
ribosomal binding site• No tRNA has a corresponding anticodon for
the stop codon• Proteins called release factors bind to the
ribosome• mRNA and polypeptide are released
Gene Transcription
Transcribed DNA winds up again
DNA to be transcribed unwinds
mRNAtranscript
RNA polymerase
Growing RNA transcript
5’
3’ 5’
3’
Direction of transcription
Transcript Modificationunit of transcription in a DNA strand
exon intron
mature mRNA transcript
poly-A tail
5’
5’ 3’
3’
snipped out
snipped out
exon exonintron
cap
transcription into pre-mRNA
3’ 5’
Genetic Code• Set of 64 base triplets
– 4 bases, 3 positions– Ie. 4 x 4 x 4 = 64
• Codon– Sets of nucleotide bases
read in blocks of three
• 61 specify amino acids
• 3 stop translation – Stop Codons
• Twenty kinds of amino acids are specified by 61 codons
• Most amino acids can be specified by more than one codon
• Example: Six codons specify leucine– UUA, UUG, CUU, CUC, CUA,
CUG
codon in mRNA
anticodon in tRNA
amino acid OH
tRNA molecule’s attachment site for amino acid
tRNA Structure
Elongation
A (second binding site for tRNA)Binding site for mRNA
P (first binding site for tRNA)
Polysome
• A cluster of many ribosomes translating one mRNA transcript
• Transcript threads through the multiple ribosomes like the thread of bead necklace
• Allows rapid synthesis of proteins
What Happens to the New Polypeptides?
• Some just enter the cytoplasm
• Many enter the endoplasmic reticulum and move through the cell membrane system where they are modified
Don’t Worry About it Till After Test #1 !Don’t Worry About it Till After Test #1 !
Ove
rvie
w Transcription
Translation
mRNA rRNA tRNA
Mature mRNA transcripts
ribosomal subunits
mature tRNA
SUMMARYCLIP
TRANSLATIONCLIP
When Things Go WrongMutations:
Base-Pair SubstitutionsInsertionsDeletions
Frameshift Mutations• Insertion-Extra base added into
gene region• Deletion-Base removed from
gene region• Both shift the reading frame• Result in many wrong amino
acids
Effect of Mutations on DNA vs. RNA?
original base triplet in a DNA strand
As DNA is replicated, proofreadingenzymes detect the mistake andmake a substitution for it:
a base substitution within the triplet (red)
One DNA molecule carries the original, unmutated sequence
The other DNAmolecule carries a gene mutation
POSSIBLE OUTCOMES:
OR
ARGININE GLYCINE TYROSINE TRYPTOPHAN ASPARAGINE
ARGININE GLYCINE LEUCINE GLUTAMATELEUCINE
mRNA
PARENTAL DNA
amino acid sequence
altered mRNA
BASE INSERTION
altered amino acid sequence
Mutation Rates
• How often do mutations happen– Cell type– Gene type
• Only mutations in germ (sex) cells are be passed to the next generation
• Mutations in somatic cells stay in the body they happen in
Genetic Diseases and CancersGenetic Diseases and Cancers
Lecture 6: Diabetes, sugar, and ATP
Objectives
Understand how sugar metabolism works
Understand how to make ATP
Understand where sugar comes from
Understand how sugar metabolism affects you
Key Termsmetabolism, gradient, equilibrium, phosphorylation, ATP, ADP
electron transport, glycolysis, insulin, glycogen, glucagon
NEXT WEEK:
Cell Division and Cancer
Leading Causes of Deaths1. Heart Disease: 700,142
2. Cancer: 553,768
3. Stroke: 163,538
4. Lung diseases: 123,013
5. Accidents (unintentional injuries): 101,537
6. Diabetes: 71,372
7. Influenza/ Pneumonia: 62,034
8. Alzheimer's disease: 53,852
9. Kidney Disease: 39,480
10. Septicemia (infection): 32,238
(Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm
I don’t have to worry about that stuff till I get old!
All races, both sexes, 20–24 years1. Accidents (unintentional injuries) 2. Assault (homicide) 3. Intentional self-harm (suicide)4. Cancer 5. Heart disease 6. Genetic abnormalities7. Human immunodeficiency virus (HIV)8. Stroke 9. Influenza and pneumonia 10. Diabetes
Relative to the national population of 20-24’s, are MSU students less likely to die from the top 3?
It’s difficult for one to prevent bad luck, or
being a victim?
Two Types of Diabetes
Type 1 • Juvenile diabetes• Autoimmune
disease– Beta cells in
pancreas are killed by defense responses
• Treated with insulin injections
Type 2• Adults affected• Insulin sensing
system impaired.• Beta cells stop making
insulin.– Pancreas burns out
• Treated with diet, drugs
Diabetes Mellitis
• Cells in muscles, liver and fat don’t use insulin properly
• Disease in which excess glucose accumulates in blood, then urine
• Signs and Symptoms– Excessive urination– Constant thirst and or hunger– Fatigue– Weight loss– Blurred vision– Sores that don’t heal
Risk Factors• Age• Overweight• Inactive (exercise > 3x/week)• Family history: African, American Indian,
Asian, Pacific Islander, Hispanic or Latino descent.
• Siblings or parents have diabetes• Gestational diabetes• Blood pressure over 140/90• HDL (good) cholesterol is low and
triglicerides are high
Reducing Risks
• Physical activity- 30 min 5 days/week
• Diet Modification– Low fat- 25% of calories max– Low alcohol
• Maintain Reasonable body mass– No crash diets– Modify dietary intake
Control of Glucose Metabolism
insulin
Glucose rises
Glucose falls
Glucose is absorbed
Cells use glucose
glucagonGlycogen to glucose
Glucose uptake Glucose to
glycogen
KrispyKreme Donuts (12)
Energy from Macromolecules• Carbohydrate
• Glycogen
• Protein
• Lipids (fat)
carbohydrates
proteins
EPITHELIALCELL
INTERNALENVIRONMENT
bile salts
FATGLOBULES EMULSIFICATION
DROPLETS
bile salts
+
MICELLES
CHYLOMICRONS
Absorption Mechanisms•Food is broken down to macro molecules•Macro molecules are disassembled by enzymes in the intestines•Actively transported across membrane:
–Monosaccharides–Amino acids
•Nutrients diffuse from gut cells into blood stream
Energy from MacromoleculesEnergy Reserves• Glycogen is about 1 % of the body’s energy
reserve• Proteins is 21% of energy reserve• Fat makes up the bulk of reserves (78 %)Carbohydrate Breakdown and Storage• Glucose is absorbed into blood• Pancreas releases insulin• Insulin stimulates glucose uptake by cells• Cells convert glucose to glucose-6-
phosphate– Phosphate, functional group,
phosphorylation• This traps glucose in cytoplasm where it can
be used for glycolysisMaking Glycogen• If glucose intake is high, ATP-making
machinery goes into high gear• When ATP levels rise high enough,
glucose-6-phosphate is diverted into glycogen synthesis (mainly in liver and muscle)
• Glycogen is the main storage polysaccharide in animals
Using Glycogen• When blood levels of glucose decline,
pancreas releases glucagon• Glucagon stimulates liver cells to convert
glycogen back to glucose and to release it to the blood
• (Muscle cells do not release their stored glycogen. This is their stored sugar!)
Key ConceptsGlucose Storage1. Glucose is used to make ATP first2. When ATP store is full, glucose is stored3. Glycogen is a big branched polymer of
stored glucose– Glycogen isn’t very soluble so it is
trapped inside the cell where it is stored.
Energy from Macromolecules
Energy from Proteins• Proteins are broken down to
amino acids and the amino acids are broken down
• Amino group is removed, ammonia forms, is converted to urea and excreted
• Carbon backbones can enter the Krebs cycle or its preparatory reactions
Key Concept: Proteins can be used to make ATP in Krebs Cycle
Energy from Fats (lipids)• Most stored fats are triglycerides• Triglycerides are broken down to
glycerol and fatty acids • Fatty acids are broken down and
converted to two carbon blocks that enter the Krebs cycle (acetyl CoA)
• Key Concept: Fatty acids are used to make ATP.Conversion is slow, 2C’s at a timeBefore it can even enter Krebs Cycle
Key Concept: Contraction as well as many other cellular processes require lots of energy
• Muscle cells require huge amounts of ATP energy to power contraction
• The cells have only a very small store of ATP• There are three pathways muscle cells use
to get ATPATP Is Universal Energy Source• Photosynthesizers get energy from the sunAnimals get energy second- or third-hand from
plants or other organismsRegardless, the energy is converted to the
chemical bond energy of ATPMaking ATP• Plants make ATP during photosynthesis• Cells of all organisms make ATP by breaking
down carbohydrates, fats, and protein
Two Main Pathways for making ATP
Anaerobic pathways
FAST• Don’t require oxygen
• Start with glycolysis in cytoplasm
• Completed in cytoplasm
Aerobic pathways
SLOW• Require oxygen
• Start with glycolysis in cytoplasm
• Completed in mitochondria
(Note: special membrane and gradient)
Overview of Aerobic RespirationCYTOPLASM
MITOCHONDRION
GLYCOLYSIS
ELECTRON TRANSPORT
PHOSPHORYLATION
KREBS CYCLE ATP
ATP
energy input to start reactions
2 CO2
4 CO2
2
32
water
2 NADH
8 NADH
2 FADH2
2 NADH 2 pyruvate
e- + H+
e- + oxygen
(2 ATP net)
glucose
TYPICAL ENERGY YIELD: 36 ATP
e-
e- + H+
e- + H+
ATP
H+
e- + H+
Main Pathways Start with Glycolysis• Glycolysis occurs in cytoplasm• Reactions are catalyzed by enzymes• Glucose 2 Pyruvate
(six carbons) (three carbons)
Overview of Aerobic RespirationC6H1206 + 6O2 6CO2 + 6H20glucose oxygen carbon water
dioxide
Summary of Energy Harvest (per molecule of glucose)
• Glycolysis– 2 ATP formed by substrate-level
phosphorylation• Krebs cycle and preparatory reactions
– 2 ATP formed by substrate-level phosphorylation
• Electron transport phosphorylation– 32 ATP formed
Efficiency of Aerobic Respiration• 686 kcal of energy are released
• 7.5 kcal are conserved in each ATP
• When 36 ATP form, 270 kcal (36 X 7.5) are captured in ATP
• Efficiency is 270 / 686 X 100 = 39 percent
• Key Concept: Most energy is lost as heat
Overview of Aerobic RespirationCYTOPLASM
MITOCHONDRION
GLYCOLYSIS
ELECTRON TRANSPORT
PHOSPHORYLATION
KREBS CYCLE ATP
ATP
energy input to start reactions
2 CO2
4 CO2
2
32
water
2 NADH
8 NADH
2 FADH2
2 NADH 2 pyruvate
e- + H+
e- + oxygen
(2 ATP net)
glucose
TYPICAL ENERGY YIELD: 36 ATP
e-
e- + H+
e- + H+
ATP
H+
e- + H+
Aerobic RespirationCoenzyme ProductionKey Concepts: Coenzyme production1.Kreb’s cycle produces activated coenzymes
2.Coenzymes push electron transport Electron Transport• Occurs in the mitochondria• Coenzymes deliver electrons to electron transport systems
• Electron transport sets up H+ ion gradients
• Flow of H+ down gradients powers ATP formation The final electron acceptor is oxygen
Importance of Oxygen• Electron transport phosphorylation requires the presence of oxygen
• Oxygen withdraws spent electrons from the electron transport system, then combines with H+ to form water
What’s the deal with Oxygen?electron transport chain over simplified
Key concept: If you pull water apart, it really wants to get back together again
• By giving the Oxygen atom in water an electron, it will give you a proton, which is actually a H+
• Oxygen is the final electron acceptor?How it Works:1.Pull a hydrogen off a water (HOH to OH-)2.Pull the hydrogen (H+) across a membrane
(electrochemical GRADIENT)3.Make the H+ do work on its way back to
OH-
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Fermentation Pathways• Begin with glycolysis• Do not break glucose down completely
to carbon dioxide and water• Yield only the 2 ATP from glycolysis• Steps that follow glycolysis serve only
to regenerate NAD+
Yeasts• Single-celled fungi• Carry out alcoholic fermentation• Saccharomyces cerevisiae
– Baker’s yeast– Carbon dioxide makes bread
dough rise • Saccharomyces ellipsoideus
– Used to make beer and wine• MSU hard cider project:
Sacchromyces banyan DV10
Anaerobic Pathways• Do not use oxygen• Produce less ATP than aerobic pathways• Two types
– Fermentation pathways• The burn• The Buzz
– Anaerobic electron transport
Anaerobic Electron Transport• Carried out by certain bacteria• Electron transport system is in bacterial
plasma membrane • Final electron acceptor is compound from
environment (such as nitrate), NOT oxygen– Doesn’t require Oxygen– Can’t work with Oxygen
• ATP yield is low• Lets bacteria live where other organisms
can’t
Lactate Fermentation
C6H12O6
ATP
ATPNADH
2 lactate
electrons, hydrogen from NADH
2 NAD+
2
2 ADP
2 pyruvate
2
4
energy output
energy input
GLYCOLYSIS
LACTATE FORMATION
2 ATP net
Alcoholic Fermentation
C6H12O6
ATP
ATPNADH
2 acetaldehyde
electrons, hydrogen from NADH
2 NAD+
2
2 ADP
2 pyruvate
2
4
energy output
energy input
GLYCOLYSIS
ETHANOL FORMATION
2 ATP net
2 ethanol
2 H2O
2 CO2
Animals Can’t do this!
Processes Are Linked Aerobic Respiration
• Reactants
– Sugar
– Oxygen
• Products
– Carbon dioxide
– Water
Photosynthesis
• Reactants
– Carbon dioxide
– Water
• Products
– Sugar
– Oxygen
ATP Formation in Plants
• When water is split during photolysis, hydrogen ions are released into thylakoid compartment. (Electrochemical GRADIENT)
• More hydrogen ions are pumped into the thylakoid compartment when the electron transport system operates
ATP Formation• Electrical and H+
concentration gradient exists between thylakoid compartment and stroma
• H+ flows down gradients into stroma through ATP synthesis
• Flow of ions drives formation of ATP
Summary of Photosynthesis
light6O2
12H2O
CALVIN-BENSON CYCLE
C6H12O6
(phosphorylated glucose)
NADPHNADP+ATPADP + Pi
PGA PGAL
RuBP
P
6CO2
end product (e.g. sucrose, starch, cellulose)
LIGHT-DEPENDENT REACTIONS
Two Important Pathways
Light Reaction• Makes ATP from light
energyDark Reaction• Makes glucose by
burning ATP• Uses CO2 from the air
and water to make glucose
Machinery of Noncyclic Electron Flow
photolysis
H2O
NADP+ NADPH
e–
ATP
ATP SYNTHASE
PHOTOSYSTEM IPHOTOSYSTEM II ADP + Pi
e–
Lecture 7: Cell Division and CancerLecture 7: Cell Division and Cancer
Objectives:
Understand basic concepts of cancer
Understand cell division
Understand how cell division is regulated
Understand programmed cell death
Key Terms: Mitosis, interphase, tumor, metastasis, angiogenesis, neoplasm, benign, malignant, adenoma, carcinoma, tumor suppressor, growth factor, check point, oncogene, programmed cell death
Leading Causes of Death
Total US Population• Heart Disease• Cancer• Stroke• Lung diseases• Accidents• Diabetes• Flu and Pneumonia• Alzheimer's disease• Kidney Disease• Infections
(Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm
US Population 20-24 • Accidents• Homicide • Suicide• Cancer • Heart disease • Genetic Disease• HIV (AIDS)• Stroke • Flu and Pneumonia
• Diabetes
Leading Sites of New Cancer and Deaths 2003 estimates
Male New cases DeathsProstate 220,900 28,900Lung 91,800 88,400Colon 72,800 28,300Bladder 42,200 8,600Melanoma 29,900 na
Female New cases DeathsBreast 211,300 39,800Lung 80,100 68,800Colon 74,700 28,800Uterine 40,100 6,800Ovary 24,400 14,300
Cancer
Features of Cancer Cells
1. Make their own growth signals
2. Insensitive to growth stopping signals
3. Insensitive to self destruct signals
4. Immortal ! : unlimited replication
5. Stimulate new blood vessel growth
6. Invasive : move out of tumor
How does Cancer Start?Cellular Damage Control
Normal cells protect their DNA Information
Damage control system
1.Detect DNA and cellular damage
2.Stop cell division (prevent replication of damage)
3.Activate damage repair systems
4.Activate self destruct system
DAMAGEEVENT
Stop Cell DivisionActivate Damage RepairDamage Assessment
Repair is Successful
Mild to Moderate DamageSevere
Damage
Programmed Cell Death
RepairFails
Damage AccumulationLeads to Cancer
##
Tumor
• An abnormal mass of undifferentiated cells
• It often interferes with body functions
• It can absorb nutrients needed elsewhere
• It can be benign, grow slowly and stay in one area.
• It can be malignant, grow rapidly and spread to other parts of the body
Cancer Terminology• Neoplasm-Cells that have no potential to spread to and
grow in another location in the body
• Benign-Non-cancerous growth that does not invade nearby tissue or spread
• Malignant-growth no longer under normal growth control
• Metastasis-spread of cancer from its original site to another part of the body
• Adenoma-A benign tumor that develops from glandular tissue
• Carcinoma-A tumor that develops from epithelial cells, such as the inside of the cheek or the lining of the intestine
Understanding Cancer
To understand cancer, you must understand three fundamental cellular processes
1.Cell Division2. Gene Regulation
3. Programmed Cell Death
Cell Division• Key concepts of Cell Division1. Cell Cycle2. DNA Replication3. Chromosome Division4. Cell Division• There are two types of cell divisionMitosis – for growing, results in two
identical cells.Meiosis – for sexual reproduction, results
in four cells with only one copy of chromosomes
Cell Cycle• Cycle starts when a new cell forms• During cycle, cell increases in mass
and duplicates its chromosomes• Cycle ends when the new cell dividesKey Terms: Cell Cycle, Chromosomes, Cell
Division
Control of the Cycle• Once S begins, the cycle
automatically runs through G2 and mitosis
• The cycle has a built-in molecular brake in G1 (p53 tumor suppressor)
• Cancer involves a loss of control over the cycle, malfunction of the “brakes”
Interphase: Phase between division and starting division again.Three intervals of Interphase1. G1 1st Growth phase- cell makes parts, and does normal
things2. S Synthesis phase- DNA replication3. G2 2nd Growth phase- making parts for cell division
4. G0 Zero Growth phase• Like getting stuck in park• Terminal development
Key Concept:At each step, the cell must
be in orderLongest part of the cycleCell mass increasesCytoplasmic components doubleDNA is duplicated
Decoding the Cell Cycle
G1 S
INTERPHASE
G2
Key Concept:
• During mitosis each cell gets a high fidelity copy of each chromosome
• Multiple check points prevent run-away cycling
Cancer cells are in run-away mode, the checkpoints are broken or ignored
Cell DivisionMitosis
Stupmer? also… Key Concept:
• Each chromosome has two strands of DNA
• Each chromosome has one copy of each
gene*
• Each somatic cell has two of each
chromosome
• Each somatic cell has two copies of each
gene*
*assume single copy genes
Chromosomes
DNA and proteinsarranged as cylindrical fiber
DNA
Histone
Nucleosome
Chromosome: A double stranded DNA molecule & attached proteins
Almost no naked DNA
Chromosome (unduplicated)
Chromosome (duplicated)
Gene RegulationOncogenesGenes who’s products transform normal cells
into cancer cells.– Required for normal cell cycling– Products of these genes are no longer
regulated – “gain of function”
Tumor suppressorsProteins that prevent the progression of the cell
cycle– P53 is a DNA binding protein that
recognizes damaged DNA and stops DNA replication
– “loss of function”Imortalization• Normal cells only divide about 50 times in a
petri dish (if you can get them to divide)• Cancer cells just keep dividing (HeLa and
MCF-7 cells)• Telomers (ends of chromosomes) usually
spell the end for normal cells, but they don’t wear out
Growth Factors• Signaling molecules that enhance cell division• Activate “cascade” of signaling inside cell• Hyperactive cascade members can trigger cell
division by turning genes on at the wrong time• Hyperactivity lets cells ignore regulatory
signals
Anchorage dependent cell cycle arrest• Adhesion is required for normal cell division
rates• Cancer cells loose cell adhesion molecules• Cancer cells don’t respond to limiting signalsAngiogenesis• Blood vessel formation• Cancer cells trick blood vessels into
supplying nutrients• Cancer cells secrete the growth factors that
they are using
Gene Regulation
Gene Regulation
Cancer and Smoking
• The smoke from a cigarette contains about 1010 particles/ml
and 4800 chemical compounds
• There are over 60 carcinogens in cigarette smoke that have been evaluated for which there is 'sufficient evidence for carcinogenicity' in either laboratory animals or humans
• These compounds damage DNA in the cells of the lung. The mechanism behind the damage is unknown.
• Damage leads to mutations
Smoking and Cancer• The kicker
– Somehow p53 gets more mutations than other randomly selected sites
– The mutations keep p53 from binding to DNA
– This means that p53 can no longer prevent DNA replication when there is other damage
x xxDNA
TranscriptionTranslation
p53
STOP
mp53
GO
MUTANTMUTANT NORMALNORMALDNA
DNA
Colon Cancer Progression
The cell death program1. Activated by cell surface receptors2. Makes pores in Mitochondria3. DNA is chopped up4. Blebbing (not popping)5. Adsorption by neighbors • Nematodes, frog tails,
webbed fingers, and HIVKey ConceptsCells are caused to die on purposeTwo examples: Epithelial cells, Damaged cellsBased on a balance of protecting proteins and killing proteins.Cancer cells often have high levels of protecting proteins.AKA: Apoptosis
Colon Cancer• Crypt• Polyp• Malignant polyp
Programmed Cell Death
“The Cancer has Spread”Two linked processes• Metastasis• AngiogenesisKey concept: Metastasized cancer cells require
angiogenesis to produce another malignant tumor
• Angiogenesis- formation of new blood vessels
• Metastasis- migration of cancer cells to a new location
MetastasisCancer cells leave the tumor and establish new
colonies in other tissuesAngiogenesisDepends on growth factors released by the
invading cancer cells
Markers for Cancer• Markers are proteins found in blood• Levels markers correlates with certain
cancer types• Some tumor markers are antigens,
others are enzymes.• Example: prostate-specific antigen
(PSA) is a marker for prostate cancer in males
Angiogenesis
Angiogenesis and Metastasis
• Growing cells in culture allows researchers to investigate processes and test treatments without danger to patients
• Most cells cannot be grown in culture
Cancer Research
Henrietta Lacks
HeLa Cells