2. Mid Term #1 Study Guide 1

3. 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 system 2.Nothing interferes with the system 3.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

4. Scientific Reasoning (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

5. 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

6. Deduction Process 1.Statement of problem 2.Hypothesis as to the cause of the problem 3.Experimental tests for each hypothesis 4.Predict results (how to accept or reject the hypothesis 5.Observe results 6.Draw conclusions from the results (accept or reject the hypothesis) Premis Fundamental Assumptions Must be both valid and true Good tests Prediction is logically deducible Prediction is improbable Prediction is verifiable

7. Deductive Process Problem Hypothesis Test Prediction Observation Conclusion Class is too large If I make this confusing, then some students will drop Deliver miserable Lecture about logic Some people will get confused and drop Accept Reject Observation? No Drops Loads-O-Drops Reject Accept Was This a Good Example?

8. Deduction Premis, Fundamental Assumptions Must be both valid and true Good tests Prediction is logically deducible Prediction is improbable Prediction is verifiable

9. Facts acquired through observation Laws and theories Predictions and explanations Induction Deduction Hypothetico-Deductive Method

10. Deductive Falsification (Conjectures and Refutations) Positivist- –Only has supporting evidence –Ignores evidence against

11. The Process of Popperian Falsification 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?

12. Objectivism vs. Subjectivism Role of the Scientist Understanding 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 Values Scientific 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.

13. Objectivism and Subjectivism result in at least three concurrent views of science 2- Postmodern Relativism2- Postmodern Relativism Plurality of TruthsPlurality of Truths Science is only one form of Subjective Truth Science has made errors in the past,Science has made errors in the past, Therefore, science and scientists should be: Questioned, Evaluated and RegulatedQuestioned, Evaluated and Regulated Subjectivism holds that science and scientists are not objective, but antecedents to surroundings, training, personal experience, etc. 1- Scientific Imperialism Science is the Truth ArbiterScience is the Truth Arbiter Therefore, anything goes if scientists say soTherefore, anything goes if scientists 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- Godisms Mankind 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.

14. 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

15. Kuhn’s Scientific Revolution Prescience Crisis Normal ScienceRevolution A Scientific Theory is likea pitcher of water. When one Theory fails its components often flow into another Theory. Scientific knowledge is dynamic and changes with new discoveries and additions of new information

16. Lecture 1: What is Science wrap-up and societyHuman endeavor dependent on the scientific community and society. we have.Not infallible, often guided by scientific fads, yet the best 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.

17. Lecture 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

18. What Is Life Properties of Life Dynamic = changingDynamic = changing Adaptability Contain Information (DNA)Contain Information (DNA) Ordered StructureOrdered Structure Uniformity of class Definition of Life An organismic state characterized by the capacity for metabolism, growth, reaction to stimuli, and reproduction.An organismic state characterized by the capacity for metabolism, growth, reaction to stimuli, and reproduction. A principle or force that underlies the distinctive quality of animate beings.A principle or force that underlies the distinctive quality of animate beings. The quality that distinguishes a vital and functional organism from inanimate objects.The quality that distinguishes a vital and functional organism from inanimate objects. Characteristics of Death Absence of life Total and permanent cessation of all vital (living) functionTotal and permanent cessation of all vital (living) function Absence of the characteristics of lifeAbsence of the characteristics of life Key Terms in “Life” Definition MetabolismMetabolism –Acquires and expends “energy” GrowthGrowth –Makes what it needs ReactionReaction –Senses Environment ReproductionReproduction –A population of one and only one is going to run into trouble sooner than later Smallest Components of Life Elements (atoms)Elements (atoms) MoleculesMolecules MacromoleculesMacromolecules –Information carriers Enzymes, proteinsEnzymes, proteins –Functional capacity Membranes and wallsMembranes and walls –Boundaries, and containers

19. Categories of life’s components Atoms, Amino Acids, Macromolecules, Organelles, Cells, Cells, Organ, Systems, Symbiotic organisms, Individual, Populations Life Quantitatively Complexity –High –Low Assignment: Learn the metric measuring system and life sizes How Biologists Measure Size: Metrics

20. How simple can life be? HIV Phytoplasma and Mycoplasma = simplest cell, lack a cell wall, DNA for 200 functions (walking pneumonia, STD’s) Not 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 mycoplasma Is each of these really alive? Are they independent? Can they reproduce or metabolize on their own?

21. Organizing Life SystematicsTaxonomyCladisticsPhylogenics Methods of ClassificationMethods of Classification –Based on some relevant distinguishing characteristic –It should be meaningful –It should not be arbitrary Basis of ClassificationsBasis of Classifications –Morphological characteristics Types of structures, Size, Diet, ReproductionTypes of structures, Size, Diet, Reproduction –Molecular characteristics Mitochondrial DNAMitochondrial DNA Nuclear DNANuclear DNA Classification Kingdom Phylum Class Order Family Genus SpeciesClassification The 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).

22. So Who’s Related DNA 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.

23. Functions of Life Four categories for organizing the characteristic of life: Metabolism, Growth, Reaction, Reproduction Metabolism Storing and releasing energyStoring and releasing energy Converting light energy into chemical energyConverting light energy into chemical energy Plants fix carbon from the airPlants fix carbon from the air Animals release carbon from storage molecluesAnimals release carbon from storage molecluesGrowth Using the stored energy Incorporating acquired materials Catabolic processes- breaking down Anabolic processes- building up Reaction Sensing environment –Receptors andMetabolic changes Reacting to changing environment Examples from Bacteria, Plants and Animals Reacting to internal environment: HomeostasisReproduction Sexual Reproduction: Cell Process: Meiosis and Mixing Genes Replication, Division: Cell Process: Mitosis and High fidelity copies Adaptation and Selection

24. 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 Story The 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 Process Chance, Necessity, and Self Organization Chemical processes generated life precursors Precursors assembled into proto cells Extraterrestrial deposition (Panspermia) Organisms came from somewhere else Chemistry came from somewhere elsePresuppositions Do 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?

25. Origin of Life Where did it come from? New ideas, new questions Matter, Energy, and Information Where does the information come from? Identifying Life Does 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 Summary DefinitionsProperties CharacteristicsOrganization Life and EnergyMeasuring Life Forms of Simple LifeOrigin of Life

26. Lecture 3: Chemistry of Life

27. Chemical Bonds

28. Elements Fundamental forms of matter Can’t be broken apart by normal means Most Common Elements in Living Organisms: Oxygen, Hydrogen, Carbon, and Nitrogen What Are Atoms? Smallest particles that retain properties of an element Made up of subatomic particles: –Protons (+) –Electrons (-) –Neutrons (no charge) Atomic Number Atomic Mass Isotopes and Radioisotopes Uses of Radioisotopes Tracers, Imaging, Radiation therapy HYDROGEN

29. What Determines Whether Atoms Will Interact? Electrons 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 Vacancies Unfilled shells make atoms likely to react Hydrogen, carbon, oxygen, and nitrogen all have vacancies in their outer shells Chemical Bonds, Molecules, & Compounds Bond is union between electron structures of atoms Atoms bond to form molecules Molecules may contain atoms of only one element - O 2 Molecules of compounds contain more than one element - H 2 O

30. Chemical Bonds Electrostatic Covalent 1. Ionic Bonding 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 Formation Atom has equal number of electrons and protons - no net charge Atom loses electron(s), becomes positively charged ion Atom gains electron(s), becomes negatively charged ion SODIUM ATOM 11 p + 11 e - SODIUM ION 11 p + 10 e - electron transfer CHLORINE ATOM 17 p + 17 e - CHLORINE ION 17 p + 18 e -

31. Chemical Bonds 2. Covalent Bonding 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-polar Covalent Atoms share electrons equally Nuclei of atoms have same number of protons Example: Hydrogen gas (H-H) Polar 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

32. Example + O HH slight negative charge at this end slight positive charge at this end molecule has no net charge ( + and - balance each other) KEEP YOUR EYE ON THE ELECTRONS

33. Hydrogen 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.

34. Hydrogen bond figure - - - +- Like Charge Atoms Repel Each Other Opposite Charge Atoms Attract Each Other KEEP YOUR EYE ON THE ELECTRONS

35. one large molecule another large molecule a large molecule twisted back on itself Hydrogen bonds are the most physiologically relevant chemical bond 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

36. Water Properties of Water Polarity Temperature-Stabilizing Cohesive Solvent Molecule has no net charge Water Is a Polar Covalent Molecule Oxygen end has a slight negative charge Hydrogen end has a slight positive charge Hydrophilic & Hydrophobic Hydrophilic substances –Polar –Hydrogen bond with water –Example: sugar Hydrophobic substances –Nonpolar –Repelled by water –Example: oil Water 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

37. The pH Scale and pH in general Measures H + concentration of fluid Change of 1 on scale means 10X change in H + concentration Highest H + Lowest H + 0---------------------7-------------------14 Acidic Neutral Basic Hydrogen Ions: H+ Unbound protons Have important biological effects Form when water ionizes Acids Donate H+ when dissolved in water Acidic solutions have pH < 7 Strong acids forcefully give up H+ Bases Accept H+ when dissolved in water Acidic solutions have pH > 7 Strong bases forcefully take H+ The problem with water is a static view H 3 O + ↔H 2 O↔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

38. Organic Compounds Carbon’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 backbone Functional Groups Atoms or clusters of atoms that are covalently bonded to carbon backbone Give organic compounds their different properties Examples of Functional Groups Hydroxyl group - OH Amino group- NH 3 + Carboxyl group- COOH - Phosphate group - PO 3 - Sulfhydryl group - SH Hydrogen and other elements covalently bonded to carbon: Carbohydrates, Lipids, Proteins, Nucleic Acids

39. Types of Reactions Functional 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

40. THE MACRO MOLECULES Carbohydrates 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

41. + H 2 O glucosefructose sucrose glucosefructose

42. THE MACRO MOLECULES Lipids 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 acidoleic acidlinolenic acid Triglycerides Fatty acid(s)

43. Phospholipids Main components of cell membranes

44. Sterols and Derivatives No fatty acids Rigid backbone of four fused-together carbon rings Cholesterol - most common type in animals

45. Waxes Long-chain fatty acids linked to long chain alcohols or carbon rings Firm consistency, repel water Important in water-proofing

46. THE MACRO MOLECULES Amino Acids Properties 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

47. THE MACRO MOLECULES Protein Protein Shapes Fibrous proteins –Polypeptide chains arranged as strands or sheets Globular proteins –Polypeptide chains folded into compact, rounded shapes Protein 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 chains Primary 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 sheet Tertiary Structure Folding as a result of interactions between R groups The 3D structure of a protein Quaternary Structure Some proteins are made up of more than one polypeptide chain Structure of a protein when it is folded with other polypeptides Polypeptides With Attached Organic Compounds Lipoproteins –Proteins combined with cholesterol, triglycerides, phospholipids Glycoproteins –Proteins combined with oligosaccharides

48. Examples of Secondary Structure

49. heme group coiled and twisted polypeptide chain of one globin molecule Hemoglobin

50. Denaturation Disruption of three-dimensional shape Breakage of weak bonds Causes of denaturation: –pH –Temperature Destroying protein shape disrupts function

51. A Permanent Wave hair wrapped around cuticles different bridges form bridges broken hair’s cuticle keratin macrofibril one hair cell microfibril (three chains coiled into one strand) coiled keratin polypeptide chain

52. A brief survey of a some protein types Structural Muscle Binding Signaling Storage protein Defensive protein Transportation Enzymes

53. Structural Function: Hold together Give shape Examples: Hair Tendons Ligaments

54. Structural Function: Attachment Collagen A triple helix Collagenous fiber Macrofibril Microfibril Collagen molecule Polypeptid e chain

55. Structural Proteins Crystallins Lens Fibers KeratinActin

56. Muscle Function: Contraction Muscle Flagella Image courtesy of Dr. Fatih Uckun, Parker Hughes Institute, St. Paul, MN

57. Movement in the Cell Actin and Myosin V ATP Dependent Reaction Nature Reviews Molecular Cell Biology 2, 387-392 (2001)

58. Insulin Function: Messengers Receptors Signaling

59. Function: Store What? Expensive molecules for later use Chemical energy Ovalbumin- globular glycoprotein Storage

60. Protein for Defense Example: Antibodies Key component of immune system Label invading microbes as intruders

61. Function: Moving molecules: In side the organism Between cells Inside Cells Example: Getting O 2 to where it’s needed Hemoglobin: gives blood cells their red color… Transportation

62. Concepts in Transportation The Basic Terms Permeability Diffusion - Gradients Membrane transport –Active –Passive –Bulk

63. Cell Membranes And Selective Permeability (Think Grapefruit!) O 2, CO 2, H 2 O,and small non-polar molecules Sugar, and other large, polar molecules I ions such as H +, Na +, CI -, Ca ++ X Gradients- Unequal distributions Membranes are required for gradients

64. Mechanisms of Crossing Over (the membrane) 1.Diffusion across lipid bilayer 2.Passive transport 3.Active transport 4.Bulk Transport Endocytosis Exocytosis

65. 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

66. Bulk Transport Exocytosis Endocytosis

67. Features of Enzymes Enzymes make unlikely reactions happen and happen faster Enzymes aren’t usually reactants or products and usually aren’t used up or severely 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 rearrange chemical bonds

68. Activation Energy For a reaction to occur, an energy barrier must be surmounted Enzymes make the energy barrier smaller activation energy without enzyme activation energy with enzyme energy released by the reaction products starting substance

69. Induced-Fit Model two substrate molecules active sight substrates contacting active site of enzyme TRANSITION STATE (tightest binding but least stable) end product enzyme unchanged by the reaction 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

70. Receptor Inhibitor Metabolic pathway Enzyme Hydrophobic and Hydrophillic Sterols Transport protein Pulling it all together

71. Why is Cholesterol Important? Sales of Lipitor grew 25% in 2001 to $4.4 billion. Pfizer spent $50 million on Lipitor ads last year. High cholesterol doesn’t care who you are Observational studies provide overwhelming evidence that HDL-C is an independent risk factor for coronary heart disease

72. 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

73. 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

74. Cholesterol and Health What effects your cholesterol level? Diet Exercise Genetics Age Pharmaceuticals

75. 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.

76. Statins What is a good drug anyway ? 1.Good enzyme inhibitor- a little bit goes a long way (IC 50 ) 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

77. Cholesterol Synthesis Metabolic Pathway Linear, branched or cyclic? What else do we need HMG-CoA Reductase for? Does it only affect liver cells?

78. 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

79. 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)

80. Lecture 3: Chemistry of Life Part 3 of 2 Goals: 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, protein structure, peptide bond, lipoprotein, glycoprotein, Assingment: For Tuesday, read Ch 12 and 13 For Thursday, read Ch 8 and 14

81. 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,

82. virus particle labeled with 35 S virus particle labeled with 32 P 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.

83. DNA Structure Covalent Bonds Hydrogen Bonds Nucleotide Bases (4) Adenine pairs with Thymine Guanine 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?

84. DNA Replication Summary Enzymes Topoisomerase unwinds strands DNA Polymerase attaches new complementary nucleotides DNA Ligase connects the bonds between phosphate sugar backbone of the new nucleotides Chemical Bonds Break hydrogen bonds with Topoisomerase Make Hydrogen bonds with DNA Polymerase Make covalent bonds with DNA Ligase Final 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

85. Nucleic Acids Into Proteins Same 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. RNA Ribonucleic 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 Pairs Are Different DNARNA

86. Nucleic Acids Into Proteins Three Classes of RNAs 1.Messenger RNA (mRNA)-Carries protein-building instruction 2.Ribosomal RNA (rRNA)-Major component of ribosome 3.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 complex Elongation 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

87. Gene Transcription Transcribed DNA winds up again DNA to be transcribed unwinds mRNA transcript RNA polymerase Growing RNA transcript 5’ 3’ 5’ 3’ Direction of transcription

89. Transcript Modification unit of transcription in a DNA strand exonintron mature mRNA transcript poly-A tail 5’ 3’ snipped out exon intron cap transcription into pre-mRNA 3’5’

90. 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

91. 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)

92. 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

93. 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 !

94. Overview Transcription Translation mRNA rRNAtRNA Mature mRNA transcripts ribosomal subunits mature tRNA SUMMARY SUMMARY CLIP TRANSLATION CLIP

95. When Things Go Wrong Mutations: Base-Pair Substitutions Insertions Deletions 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, proofreading enzymes detect the mistake and make a substitution for it: a base substitution within the triplet (red) One DNA molecule carries the original, unmutated sequence The other DNA molecule carries a gene mutation POSSIBLE OUTCOMES: OR ARGININEGLYCINETYROSINETRYPTOPHANASPARAGINE ARGININEGLYCINELEUCINEGLUTAMATELEUCINE mRNA PARENTAL DNA amino acid sequence altered mRNA BASE INSERTION altered amino acid sequence

96. 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 Cancers

97. 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 Terms metabolism, gradient, equilibrium, phosphorylation, ATP, ADP electron transport, glycolysis, insulin, glycogen, glucagon NEXT WEEK: Cell Division and Cancer

98. Leading Causes of Deaths 1.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

99. I don’t have to worry about that stuff till I get old! All races, both sexes, 20–24 years 1.Accidents (unintentional injuries) 2.Assault (homicide) 3.Intentional self-harm (suicide) 4.Cancer 5.Heart disease 6.Genetic abnormalities 7.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?

100. 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

101. 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

102. 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

103. 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

104. Control of Glucose Metabolism insulin Glucose rises Glucose falls Glucose is absorbed Cells use glucose glucagon Glycogen to glucose Glucose uptake Glucose to glycogen Krispy Kreme Donuts (12)

105. Energy from Macromolecules Carbohydrate Glycogen Protein Lipids (fat) carbohydrates proteins EPITHELIAL CELL INTERNAL ENVIRONMENT bile salts FAT GLOBULES 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

106. Energy from Macromolecules Energy 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 glycolysis Making 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 Concepts Glucose Storage 1.Glucose is used to make ATP first 2.When ATP store is full, glucose is stored 3.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.

107. 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 time Before it can even enter Krebs Cycle

108. 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 ATP ATP Is Universal Energy Source Photosynthesizers get energy from the sun Animals get energy second- or third-hand from plants or other organisms Regardless, the energy is converted to the chemical bond energy of ATP Making 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)

109. Overview of Aerobic Respiration CYTOPLASM MITOCHONDRION GLYCOLYSIS ELECTRON TRANSPORT PHOSPHORYLATION KREBS CYCLE ATP energy input to start reactions 2 CO 2 4 CO 2 2 32 water 2 NADH 8 NADH 2 FADH 2 2 NADH 2 pyruvate e - + H + e - + oxygen (2 ATP net) glucose TYPICAL ENERGY YIELD: 36 ATP e-e- e - + H + ATP H+H+ e - + H +

110. Main Pathways Start with Glycolysis Glycolysis occurs in cytoplasm Reactions are catalyzed by enzymes Glucose2 Pyruvate (six carbons) (three carbons ) Overview of Aerobic Respiration C 6 H 12 0 6 + 6O 2 6CO 2 + 6H 2 0 glucose 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

111. Overview of Aerobic Respiration CYTOPLASM MITOCHONDRION GLYCOLYSIS ELECTRON TRANSPORT PHOSPHORYLATION KREBS CYCLE ATP energy input to start reactions 2 CO 2 4 CO 2 2 32 water 2 NADH 8 NADH 2 FADH 2 2 NADH 2 pyruvate e - + H + e - + oxygen (2 ATP net) glucose TYPICAL ENERGY YIELD: 36 ATP e-e- e - + H + ATP H+H+ e - + H +

112. Aerobic Respiration Coenzyme Production Key Concepts: Coenzyme production 1.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 - http://www.sp.uconn.edu/~terry/images/anim/ETS.html

114. 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

115. Lactate Fermentation C 6 H 12 O 6 ATP NADH 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

116. Alcoholic Fermentation C 6 H 12 O 6 ATP NADH 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 H 2 O 2 CO 2 Animals Can’t do this!

117. Processes Are Linked Aerobic Respiration Reactants –Sugar –Oxygen Products –Carbon dioxide –Water Photosynthesis Reactants –Carbon dioxide –Water Products –Sugar –Oxygen

118. 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

119. Summary of Photosynthesis light 6O 2 12H 2 O CALVIN- BENSON CYCLE C 6 H 12 O 6 (phosphorylated glucose) NADPHNADP + ATP ADP + P i PGA PGAL RuBP P 6CO 2 end product (e.g. sucrose, starch, cellulose) LIGHT-DEPENDENT REACTIONS Two Important Pathways Light Reaction Makes ATP from light energy Dark Reaction Makes glucose by burning ATP Uses CO 2 from the air and water to make glucose

120. Machinery of Noncyclic Electron Flow photolysis H2OH2O NADP + NADPH e–e– ATP ATP SYNTHASE PHOTOSYSTEM IPHOTOSYSTEM II ADP + P i e–e–

121. Lecture 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

122. 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

123. Leading Sites of New Cancer and Deaths 2003 estimates Male New casesDeaths Prostate220,90028,900 Lung 91,80088,400 Colon 72,80028,300 Bladder 42,200 8,600 Melanoma 29,900 na Female New casesDeaths Breast211,30039,800 Lung 80,10068,800 Colon 74,70028,800 Uterine 40,100 6,800 Ovary 24,40014,300

124. 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

125. 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

126. DAMAGE EVENT Stop Cell Division Activate Damage Repair Damage Assessment Repair is Successful Mild to Moderate Damage Severe Damage Programmed Cell Death Repair Fails Damage Accumulation Leads to Cancer

127. ##

128. 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

129. 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

130. Understanding Cancer To understand cancer, you must understand three fundamental cellular processes 1.Cell Division 2.Gene Regulation 3.Programmed Cell Death

131. Cell Division Key concepts of Cell Division 1.Cell Cycle 2.DNA Replication 3.Chromosome Division 4.Cell Division There are two types of cell division Mitosis – 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 divides Key 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”

132. Interphase : Phase between division and starting division again. Three intervals of Interphase 1.G 1 1 st Growth phase- cell makes parts, and does normal things 2.SSynthesis phase- DNA replication 3.G 2 2 nd Growth phase- making parts for cell division 4.G 0 Zero Growth phase Like getting stuck in park Terminal development Key Concept: At each step, the cell must be in order Longest part of the cycle Cell mass increases Cytoplasmic components double DNA is duplicated Decoding the Cell Cycle G1G1 S INTERPHASE G2G2

133. 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 Division Mitosis

134. 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

135. Chromosomes DNA and proteins arranged as cylindrical fiber DNA Histone Nucleosome Chromosome: A double stranded DNA molecule & attached proteins Almost no naked DNA Chromosome (unduplicated) Chromosome (duplicated)

136. Gene Regulation Oncogenes Genes 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 suppressors Proteins 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 signals Angiogenesis Blood vessel formation Cancer cells trick blood vessels into supplying nutrients Cancer cells secrete the growth factors that they are using

137. Gene Regulation

139. Cancer and Smoking The smoke from a cigarette contains about 10 10 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

140. 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 xx DNA Transcription Translation p53 STOP mp53 GO MUTANT NORMAL DNA

141. Colon Cancer Progression The cell death program 1.Activated by cell surface receptors 2.Makes pores in Mitochondria 3.DNA is chopped up 4.Blebbing (not popping) 5.Adsorption by neighbors Nematodes, frog tails, webbed fingers, and HIV Key Concepts Cells are caused to die on purpose Two examples: Epithelial cells, Damaged cells Based 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

142. “The Cancer has Spread” Two linked processes Metastasis Angiogenesis Key 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 Metastasis Cancer cells leave the tumor and establish new colonies in other tissues Angiogenesis Depends 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

143. Angiogenesis

144. Angiogenesis and Metastasis

145. 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