1. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Metabolism  Metabolism – all chemical reactions necessary to maintain life  Cellular respiration – food fuels are broken down within cells and some of the energy is captured to produce ATP  Anabolic reactions – synthesis of larger molecules from smaller ones  Catabolic reactions – hydrolysis of complex structures into simpler ones

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings METABOLISM FURNISH THE ENERGY REQUIRED FEED BUILDING BLOCK FOR THE PROCESSES OF GROWTH, ETC CATABOLISM:DEGRADATION OF COMPLEX COMPOUNDS METABOLISM ANABOLISM: SYNTHESIS OF COMPLEX COMPOUND METABOLISHING EQUIPMENTS: CELL--- CYTOPLASM --- 50-500 MITOCHONDRIA --- ENDOPLASMIC RETICULUM --- 1000 ENZYMES

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PATHWAYS IN THE UTILISATION OF NUTRIENT: 1.LARGE MOLECULES HYDROLIZED TO SIMPLER COMPOUND 2.GLUCOSE, FATTY ACID, GLICEROL, AMINO ACIDS CONVERTED FURTHER 3.THE END PRODUCTS OF PHASE TWO CONVERTED TO CO2 AND H2O HOW ANIMAL TRAPS ENERGY FROM FEED ?: ENERGY RADIANT  GREEN PLANT  COMPLEX PLANT CONSTITUENT  INGESTED  ADP + HPO 4 _ + ENERGY  ATP METABOLISM

4. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Photosynthesis: Sun’s energy becomes part of glucose molecule energy Carbon dioxide Water Chlorophyll GLUCOSE 6 CO2 + 6 H20 + energy (sun)C6H12O6 + 6 O2

5. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings NNR-BABI-KULIAH 4

6. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Metabolism  Enzymes shift the high-energy phosphate groups of ATP to other molecules  These phosphorylated molecules are activated to perform cellular functions

7. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Stages of Metabolism  Energy-containing nutrients are processed in three major stages  Digestion – breakdown of food; nutrients are transported to tissues  Anabolism and formation of catabolic intermediates where nutrients are:  Built into lipids, proteins, and glycogen  Broken down by catabolic pathways to pyruvic acid and acetyl CoA  Oxidative breakdown – nutrients are catabolized to carbon dioxide, water, and ATP

8. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Stages of Metabolism Figure 24.3

9. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Oxidation-Reduction (Redox) Reactions  Oxidation occurs via the gain of oxygen or the loss of hydrogen  Whenever one substance is oxidized, another substance is reduced  Oxidized substances lose energy  Reduced substances gain energy  Coenzymes act as hydrogen (or electron) acceptors  Two important coenzymes are nicotinamide adenine dinucleotide (NAD + ) and flavin adenine dinucleotide (FAD)

10. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP  ATP is synthesized via substrate-level phosphorylation in glycolysis and the Krebs cycle Figure 24.4a Mechanisms of ATP Synthesis: Substrate-Level Phosphorylation

11. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Uses the chemiosmotic process whereby the movement of substances across a membrane is coupled to chemical reactions Mechanisms of ATP Synthesis: Oxidative Phosphorylation

12. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Is carried out by the electron transport proteins in the cristae of the mitochondria  Nutrient energy is used to pump hydrogen ions into the intermembrane space  A steep diffusion gradient across the membrane results  When hydrogen ions flow back across the membrane through ATP synthase, energy is captured and attaches phosphate groups to ADP (to make ATP) Mechanisms of ATP Synthesis: Oxidative Phosphorylation

13. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24.4b Mechanisms of ATP Synthesis: Oxidative Phosphorylation

14. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Carbohydrate Metabolism  Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism  Oxidation of glucose is shown by the overall reaction: C 6 H 12 O 6 + 6O 2  6H 2 O + 6CO 2 + 36 ATP + heat  Glucose is catabolized in three pathways  Glycolysis  Krebs cycle  The electron transport chain and oxidative phosphorylation

15. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Carbohydrate Catabolism Figure 24.5

16. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis  A three-phase pathway in which:  Glucose is oxidized into pyruvic acid  NAD + is reduced to NADH + H +  ATP is synthesized by substrate-level phosphorylation  Pyruvic acid:  Moves on to the Krebs cycle in an aerobic pathway  Is reduced to lactic acid in an anaerobic environment

17. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis Figure 24.6

18. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis: Phase 1 and 2  Phase 1: Sugar activation  Two ATP molecules activate glucose into fructose-1,6-diphosphate  Phase 2: Sugar cleavage  Fructose-1,6-bisphosphate is cleaved into two 3-carbon isomers  Bishydroxyacetone phosphate  Glyceraldehyde 3-phosphate

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis: Phase 3  Phase 3: Oxidation and ATP formation  The 3-carbon sugars are oxidized (reducing NAD + )  Inorganic phosphate groups (P i ) are attached to each oxidized fragment  The terminal phosphates are cleaved and captured by ADP to form four ATP molecules

20. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis: Phase 3  The final products are:  Two pyruvic acid molecules  Two NADH + H + molecules (reduced NAD + )  A net gain of two ATP molecules

21. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids

22. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Pyruvic acid is converted to acetyl CoA in three main steps:  Decarboxylation  Carbon is removed from pyruvic acid  Carbon dioxide is released

23. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Oxidation  Hydrogen atoms are removed from pyruvic acid  NAD + is reduced to NADH + H +  Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA

24. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle  An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating:  Three molecules of NADH + H +  One molecule of FADH 2  Two molecules of CO 2  One molecule of ATP  For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle Krebs Cycle PLAY

25. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

27. Krebs Cycle Figure 24.7

28. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

29. Electron Transport Chain  Food (glucose) is oxidized and the released hydrogens:  Are transported by coenzymes NADH and FADH 2  Enter a chain of proteins bound to metal atoms (cofactors)  Combine with molecular oxygen to form water  Release energy  The energy released is harnessed to attach inorganic phosphate groups (P i ) to ADP, making ATP by oxidative phosphorylation

30. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Oxidative Phosphorylation  The hydrogens delivered to the chain are split into protons (H + ) and electrons  The protons are pumped across the inner mitochondrial membrane by:  NADH dehydrogenase (FMN, Fe-S)  Cytochrome b-c 1  Cytochrome oxidase (a-a 3 )  The electrons are shuttled from one acceptor to the next

31. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Oxidative Phosphorylation  Electrons are delivered to oxygen, forming oxygen ions  Oxygen ions attract H + to form water  H + pumped to the intermembrane space:  Diffuses back to the matrix via ATP synthase  Releases energy to make ATP InterActive Physiology ® : Muscular System: Muscle Metabolism PLAY

32. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Oxidative Phosphorylation Figure 24.8

33. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient  The transfer of energy from NADH + H + and FADH 2 to oxygen releases large amounts of energy  This energy is released in a stepwise manner through the electron transport chain

34. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient  The electrochemical proton gradient across the inner membrane:  Creates a pH gradient  Generates a voltage gradient  These gradients cause H + to flow back into the matrix via ATP synthase Electron Transport PLAY

35. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient Figure 24.9

36. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings ATP Synthase  The enzyme consists of three parts: a rotor, a knob, and a rod  Current created by H + causes the rotor and rod to rotate  This rotation activates catalytic sites in the knob where ADP and P i are combined to make ATP

37. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure of ATP Synthase Figure 24.10

38. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Summary of ATP Production Figure 24.11

39. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycogenesis and Glycogenolysis  Glycogenesis – formation of glycogen when glucose supplies exceed cellular need for ATP synthesis  Glycogenolysis – breakdown of glycogen in response to low blood glucose Figure 24.12

40. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Gluconeogenesis  The process of forming sugar from noncarbohydrate molecules  Takes place mainly in the liver  Protects the body, especially the brain, from the damaging effects of hypoglycemia by ensuring ATP synthesis can continue

41. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipid Metabolism  Most products of fat metabolism are transported in lymph as chylomicrons  Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells  Only neutral fats are routinely oxidized for energy  Catabolism of fats involves two separate pathways  Glycerol pathway  Fatty acids pathway

42. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipid Metabolism  Glycerol is converted to glyceraldehyde phosphate  Glyceraldehyde is ultimately converted into acetyl CoA  Acetyl CoA enters the Krebs cycle  Fatty acids undergo beta oxidation which produces:  Two-carbon acetic acid fragments, which enter the Krebs cycle  Reduced coenzymes, which enter the electron transport chain

43. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipid Metabolism Figure 24.13

44. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipogenesis and Lipolysis  Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides  Glucose is easily converted into fat since acetyl CoA is:  An intermediate in glucose catabolism  The starting molecule for the synthesis of fatty acids

45. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipogenesis and Lipolysis  Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse  Oxaloacetic acid is necessary for the complete oxidation of fat  Without it, acetyl CoA is converted into ketones (ketogenesis)

46. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipogenesis and Lipolysis Figure 24.14

47. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Phospholipids are important components of myelin and cell membranes Lipid Metabolism: Synthesis of Structural Materials

48. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  The liver:  Synthesizes lipoproteins for transport of cholesterol and fats  Makes tissue factor, a clotting factor  Synthesizes cholesterol for acetyl CoA  Uses cholesterol to form bile salts  Certain endocrine organs use cholesterol to synthesize steroid hormones Lipid Metabolism: Synthesis of Structural Materials

49. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Protein Metabolism  Excess dietary protein results in amino acids being:  Oxidized for energy  Converted into fat for storage  Amino acids must be deaminated prior to oxidation for energy

50. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Protein Metabolism  Deaminated amino acids are converted into:  Pyruvic acid  One of the keto acid intermediates of the Krebs cycle  These events occur as transamination, oxidative deamination, and keto acid modification