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