1. Chapter 4 Cellular Metabolism

2. ATP: Energy for Cells ATP (adenosine triphosphate) is the energy currency of cells. ATP is constantly regenerated from ADP (adenosine diphosphate) after energy is expended by the cell. Use of ATP by the cell has advantages: 1) can be used in many types of reactions. 2) When ATP → ADP + P, energy released is sufficient for cellular needs, little energy is wasted.

3. ATP is called a “high-energy” compound because a phosphate group is easily removed.

4. ATP’s structure ATP is a nucleotide made of adenine and ribose and three phosphate groups.

5. The ATP cycle

6. Function of ATP Cells make use of ATP for: Chemical work –to synthesize macromolecules Transport work –needed to pump substances across the plasma membrane (Active Transport) Mechanical work –for cellular movements

7. Two types of metabolic reactions Anabolism larger molecules are made synthesis requires energy Catabolism larger molecules are broken down decomposition releases energy – why? 4-2

8. Anabolism Why is it needed? for cellular growth and repair Dehydration synthesis type of anabolic process used to make polysaccharides, triglycerides, and proteins produces water 4-3

9. Anabolism 4-4

10. Catabolism breaks down larger molecules into smaller ones Hydrolysis a catabolic process used to decompose carbohydrates, lipids, and proteins water is used reverse of dehydration synthesis 4-5

11. Catabolism 4-6

12. Review anabolism and catabolism http://www.youtube.com/watch? v=yiuRXnyxcEA&feature=relate d

13. Review ATP http://www.youtube.com/watch? v=AhuqXwvFv2E

14. Enzymes Enzymes – biological catalysts, speed up reactions without themselves being changed Are specific – work on certain substrates Written above the reaction arrow Promotes effective collisions Does not change the overall heat of reaction Lowers the activation energy

15. Energy of activation (E a )

16. Active site – area on enzyme where substrate fits The active site may undergo a slight change in shape, called induced fit, in order to accommodate the substrate(s). The enzyme and substrate form an enzyme- substrate complex during the reaction. The enzyme is not changed by the reaction, and it is free to act again.

17. Induced fit model

18. Control of Metabolic Reactions Review - Enzymes control rates of metabolic reactions lower activation energy needed to start reactions globular proteins with specific shapes not consumed in chemical reactions substrate specific shape of active site determines substrate 4-7

19. Control of Metabolic Reactions Metabolic pathways - review series of enzyme-controlled reactions leading to formation of a product each new substrate is the product of the previous reaction Enzyme names commonly reflect the substrate have the suffix – ase sucrase, lactase, protease, lipase 4-8

20. Enzymatic reaction

21. Control of Metabolic Reactions Cofactors make some enzymes active ions or coenzymes Coenzymes organic molecules that act as cofactors vitamins Factors that affect or alter enzymes temperature radiation electricity chemicals changes in pH Will cause denaturing 4-9

22. Factors Affecting Enzymatic Speed Enzymatic reactions proceed with great speed provided there is enough substrate to fill active sites most of the time. Enzyme activity increases as substrate concentration increases because there are more collisions between substrate molecules and the enzyme.

23. Temperature and pH As the temperature rises, enzyme activity increases because more collisions occur between enzyme and substrate. If the temperature is too high, enzyme activity levels out and then declines rapidly because the enzyme is denatured. Each enzyme has an optimal pH at which the rate of reaction is highest.

24. Rate of an enzymatic reaction as a function of temperature and pH

25. Enzyme Review http://lpscience.fatcow.com/jwanamaker/ animations.htm

26. http://highered.mcgraw- hill.com/sites/0070960526/student_view0/c hapter6/animations.html http://highered.mcgraw- hill.com/sites/0070960526/student_view0/c hapter6/animations.html

27. Cellular Respiration The overall equation for cellular respiration is opposite that of photosynthesis: C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O + Energy In this reaction, glucose is oxidized and oxygen is reduced to become water. The complete oxidation of a mol of glucose releases 686 kcal of energy that is used to synthesize ATP.

28. Each reaction requires a specific enzyme. Substrate concentration, temperature, pH, and enzyme concentration affect the rates of reactions. Most metabolic pathways are regulated by feedback inhibition. Cellular respiration involves oxidation-reduction reactions and accounts for the flow of energy through all living things.

29. Cellular Respiration Occurs in three series of reactions 1.Glycolysis 2.Citric acid cycle 3.Electron transport chain Produces carbon dioxide water ATP (chemical energy) heat Includes anaerobic reactions (without O 2 ) - produce little ATP aerobic reactions (requires O 2 ) - produce most ATP 4-11

30. Overview of Cellular Respiration General purpose??

31. The oxidation of glucose is an exergonic reaction (releases energy) which drives ATP synthesis, which is an endergonic reaction (energy is required). The overall equation for cellular respiration shows the coupling of glucose breakdown to ATP buildup. The breakdown of one glucose molecule results in a maximum of 36 to 38 ATP molecules, representing about 40% of the potential energy within the glucose molecule.

32. ATP Molecules - review each ATP molecule has three parts: an adenine molecule a ribose molecule three phosphate molecules in a chain third phosphate attached by high-energy bond when the bond is broken, energy is transferred when the bond is broken, ATP becomes ADP ADP becomes ATP through phosphorylation phosphorylation requires energy released from cellular respiration 4-12

33. Cellular respiration

34. Phases of Complete Glucose Breakdown Glycolysis – the breakdown of glucose to two molecules of pyruvate (pyruvic acid) in the cytoplasm with no oxygen needed; yields 2 ATP Really – 2 ATP  4 ATP (net 2) Occurs without oxygen (anaerobic) In cytoplasm – mitochondria not needed Also called fermentation – lactic acid fermentation in us

35. Now – enter the mitochondria: Citric acid cycle – a cyclical series of oxidation reactions that give off CO 2 and produce one ATP per cycle; occurs twice per glucose molecule Electron transport system – a series of carriers that accept electrons removed from glucose and pass them from one carrier to the next until the final receptor, O 2 is reached; water is produced; energy is released and used to synthesize 32 to 34 ATP on its own

36. To review: 1. Glycolysis – in cytosol (anaerobic) 2. Citric Acid Cycle (Kreb’s Cycle) – in mitochondria (aerobic) 3. Electron Transport Chain – in mitochondria (aerobic)

37. Outside the Mitochondria: Glycolysis Glycolysis occurs in the cytoplasm and is the breakdown of glucose to two pyruvate molecules. Glycolysis is universally found in all organisms and likely evolved before the citric acid cycle and electron transport system. Glycolysis does not require oxygen.

38. Glycolysis series of ten reactions breaks down glucose into 2 pyruvic acids occurs in cytosol anaerobic phase of cellular respiration yields two ATP molecules per glucose Summarized by three main events 1. phosphorylation 2. splitting 3. production of NADH (high-energy fuel molecule) and ATP 4-13

39. Glycolysis The resulting 2 pyruvates convert into Acetyl Co- A to ready for the aerobic phases.

40. Glycolysis Event 1 - Phosphorylation two phosphates added to glucose requires ATP Event 2 – Splitting (cleavage) 6-carbon glucose split into two 3-carbon molecules 4-14

41. Glycolysis Summary Inputs: Glucose 2 NAD+ 2 ATP 4 ADP + 2 P Outputs: 2 pyruvate 2 NADH 2 ADP 2 ATP (net gain)

42. Anaerobic Reactions If oxygen is not available - electron transport chain cannot accept NADH pyruvic acid is converted to lactic acid glycolysis is inhibited ATP production declines 4-16

43. Aerobic Reactions If oxygen is available – pyruvic acid is used to produce acetyl CoA citric acid cycle begins electron transport chain functions carbon dioxide and water are formed 36 molecules of ATP produced per glucose molecule 4-17

44. Inside the Mitochondria A mitochondrion is a cellular organelle that has a double membrane, with an intermembrane space between the two layers. Cristae are folds of inner membrane that jut out into the matrix, the innermost compartment, which is filled with a gel-like fluid. The transition reaction and citic acid cycle occur in the matrix; the electron transport system is located in the cristae.

45. Transition Reaction The transition reaction connects glycolysis to the citric acid cycle, and is thus the transition between these two pathways. Pyruvate is converted to a C 2 acetyl group attached to coenzyme A (CoA), and CO 2 is released. During this oxidation reaction, NAD + is converted to NADH + H + ; the transition reaction occurs twice per glucose molecule.

46. Citric Acid Cycle The citric acid cycle is a cyclical metabolic pathway located in the matrix of the mitochondria. Each acetyl group received from the transition reaction is oxidized to 2 CO 2 molecules.

47. During the cycle, oxidation occurs when NAD + accepts electrons in three sites and FAD accepts electrons once. Substrate-level phosphorylation results in a gain of one ATP per every turn of the cycle; it turns twice per glucose. During the citric acid cycle, the six carbon atoms in glucose become CO 2. The transition reaction produces two CO 2, and the citric acid cycle produces four CO 2 per molecule of glucose.

48. Citric Acid Cycle begins when acetyl CoA combines with oxaloacetic acid to produce citric acid citric acid is changed into oxaloacetic acid through a series of reactions cycle repeats as long as pyruvic acid and oxygen are available for each citric acid molecule: one ATP is produced eight hydrogen atoms are transferred to NAD + and FAD two CO 2 produced 4-18

49. Citric acid cycle

50. Citric acid cycle inputs and outputs per glucose molecule Inputs: 2 Acetyl-Co-A 6 NAD + 2 FAD 2 ADP + 2 P Outputs: 4 CO 2 6 NADH 2 FADH 2 2 ATP

51. ATP check!!! From glycolysis – 2 ATP From citric acid cycle 2 ATP

52. Electron Transport System The electron transport system located in the cristae of mitochondria is a series of protein carriers, that pass electrons from one to the other. Electrons carried by NADH and FADH 2 enter the electron transport system. As a pair of electrons is passed from carrier to carrier, energy is released and is used to form ATP molecules by oxidative phosphorylation.

53. Oxygen receives energy-spent electrons at the end of the electron transport system. Next, oxygen combines with hydrogen, and water forms: ½ O 2 + 2 e - + 2 H + → H 2 O When NADH carries electrons to the first carrier, enough energy is released by the time electrons are accepted by O 2 to produce three ATP; two ATP are produced when FADH 2 delivers electrons to the carriers.

54. Overview of the electron transport system

55. Electron Transport Chain NADH and FADH2 carry electrons to the ETC ETC series of electron carriers located in cristae of mitochondria energy from electrons transferred to ATP synthase ATP synthase catalyzes the phosphorylation of ADP to ATP water is formed 4-19

56. Energy Yield from Glucose Metabolism – new check!! Per glucose molecule, there is a net gain of two ATP from glycolysis, which occurs in the cytoplasm by substrate-level phosphorylation. The citric acid cycle, occurring in the matrix of mitochondria, adds two more ATP, also by substrate-level phosphorylation.

57. Most ATP is produced by the electron transport system. Per glucose molecule, ten NADH and two FADH 2 take electrons to the electron transport system; three ATP are formed per NADH and two ATP per FADH 2. Electrons carried by NADH produced during glycolysis are shuttled to the electron transport chain by an organic molecule.

58. Accounting of energy yield per glucose molecule breakdown

59. Summary of Cellular Respiration 4-20

60. Review link http://www.sumanasinc.com/we bcontent/animations/content/cell ularrespiration.html

61. Summary of Catabolism of Proteins, Carbohydrates, and Fats 4-21

62. **Transparency

63. STOP

64. Carbohydrate Storage Excess glucose stored as glycogen (primarily by liver and muscle cells) fat converted to amino acids 4-22

65. Sickle-cell disease in humans

66. Cause and Repair of Mutations Mutations can be spontaneous or caused by environmental influences called mutagens. Mutagens include radiation (X-rays, UV radiation), and organic chemicals (in cigarette smoke and pesticides). DNA polymerase proof reads the new strand against the old strand and detects mismatched pairs, reducing mistakes to one in a billion nucleotide pairs replicated.

67. Transposons: Jumping Genes Transposons are specific DNA sequences that move from place to place within and between chromosomes. These so-called jumping genes can cause a mutation to occur by altering gene expression. It is likely all organisms, including humans, have transposons.

68. Cancer: A Failure of Genetic Control Cancer is a genetic disorder resulting in a tumor, an abnormal mass of cells. Carcinogenesis, the development of cancer, is a gradual process. Cancer cells lack differentiation, form tumors, undergo angiogenesis and metastasize. Cancer cells fail to undergo apoptosis, or programmed cell death.

69. Structure of DNA two polynucleotide chains hydrogen bonds hold nitrogenous bases together bases pair specifically (A-T and C-G) forms a helix DNA wrapped about histones forms chromosomes 4-25

70. RNA Molecules Messenger RNA (mRNA) - delivers genetic information from nucleus to the cytoplasm single polynucleotide chain formed beside a strand of DNA RNA nucleotides are complementary to DNA nucleotides (exception – no thymine in RNA; replaced with uracil) making of mRNA is transcription 4-26

71. RNA Molecules Transfer RNA (tRNA) - carries amino acids to mRNA carries anticodon to mRNA translates a codon of mRNA into an amino acid Ribosomal RNA (rRNA) – provides structure and enzyme activity for ribosomes 4-27

72. Protein Synthesis 4-28

73. Protein Synthesis 4-29

74. DNA Replication hydrogen bonds break between bases double strands unwind and pull apart new nucleotides pair with exposed bases controlled by DNA polymerase 4-30

75. Mutations Mutations – change in genetic information Result when extra bases are added or deleted bases are changed May or may not change the protein Repair enzymes correct mutations 4-31

76. Clinical Application Phenylketonuria PKU enzyme that breaks down the amino acid phenylalanine is missing build up of phenylalanine causes mental retardation treated by diets very low in phenylalanine 4-32