Lecture 20 metabolism &ATP Synthesis (Cellular Respiration) 913-917 in Ch.24

1. Lecture 20metabolism &ATP Synthesis(Cellular Respiration)913-917in Ch.24

2. Review Enzymes • Biological catalysts • Lower the activation energy, increase the speed of a reaction (millions of reactions per minute!)

3. How Enzymes Work • Enzymes = large protein molecules that function as biological catalysts. • Catalyst = chemical that speeds up a reaction without being consumed • NOTE: enzyme names end in –ase and are often named after their substrates • The enzyme that hydrolyzes sucrose is sucrase • Hydrolases, Add water during Hydrolysis reactions

4. Energy of activation(Ea) • There is an energy barrier that must be overcome before a chemical reaction can begin. This is called The energy of activation • Enzymes speed up the reaction by lowering the Ea barrier

5. WITHOUT ENZYME WITH ENZYME Activation energy required Less activation energy required Reactants Reactants Product Product PLAY Animation: Enzymes Figure 2.20

6. How Enzymes Work • Enzymes • Very selective • 3D shape that determines its specificity for a substrate • Substrate = the substance that the enzyme works on • Substrate binds to the enzyme in the active site • Pocket or groove on protein surface where binding occurs

7. Enzyme action Three basic steps involves in enzyme action: 1) The enzyme active site binds to the substrate. 2)The enzyme –substrate complex undergoes internal rearrangement that form the product. 3)The enzyme releases the the product of the reaction.

8. How Enzymes Work

9. Product (P)e.g., dipeptide Substrates (S)e.g., amino acids Energy isabsorbed;bond isformed. Water isreleased. Peptidebond + H2O Active site Enzyme-substratecomplex (E-S) Enzyme (E) Enzyme (E) 1 2 Substrates bindat active site.Enzyme changesshape to holdsubstrates inproper position. Internalrearrangementsleading tocatalysis occur. 3 Product isreleased. Enzymereturns to originalshape and isavailable to catalyzeanother reaction. Figure 2.21

10. Enzyme activity is affected by its environment • Temperature affects molecular motion • Enzyme’s optimal temperature is when there is the highest rate of contact between the enzyme and substrate • Temperature too high – denaturation • Changes the shape and the function of the enzyme • Salt concentration • Salt interferes with some of the chemical bonds that maintain protein shape • pH • Same is true for pH outside of the 6-8 range.eg.digestive enzyme produce in pancreas are activated in small intestine.

11. Cellular respiration

12. Chloroplasts and Mitochondria • Energy, enzymes, and membranes • Important parts of the functioning of chloroplasts and mitochondria • Photosynthesis and cellular respiration are linked

13. Same for cells

14. Phosphategroups Adenosine diphosphate Adenosine Triphosphate H2O + + P P P P P P Energy Hydrolysis Adenine Ribose ATP ADP Figure 5.4A ATP structure and hydrolysis

15. Adenosine Triphosphate (ATP) • Adenine-containing RNA nucleotide with two additional phosphate groups

16. High-energy phosphate bonds can be hydrolyzed to release energy. Adenine Phosphate groups Ribose Adenosine Adenosine monophosphate (AMP) Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) Figure 2.23

17. Function of ATP • Phosphorylation: • Terminal phosphates are enzymatically transferred to and energize other molecules • Such “primed” molecules perform cellular work (life processes) using the phosphate bond energy

18. Solute + Membrane protein (a) Transport work: ATP phosphorylates transport proteins, activating them to transport solutes (ions, for example) across cell membranes. + Relaxed smooth muscle cell Contracted smooth muscle cell Mechanical work: ATP phosphorylates contractile proteins in muscle cells so the cells can shorten. (b) + Chemical work: ATP phosphorylates key reactants, providing energy to drive energy-absorbing chemical reactions. (c) Figure 2.24

19. Metabolism • Metabolism: biochemical reactions inside cells involving nutrients • Two types of reactions • Anabolism: synthesis of large molecules from small ones • Catabolism: hydrolysis of complex structures to simpler ones

20. Metabolism • Cellular respiration: catabolism of food fuels and capture of energy to form ATP in cells • Enzymes shift high-energy phosphate groups of ATP to other molecules (phosphorylation) • Phosphorylated molecules are activated to perform cellular functions

21. Stages of Metabolism • Processing of nutrients • Digestion, absorption and transport to tissues • Cellular processing (in cytoplasm) • Synthesis of lipids, proteins, and glycogen, or • Catabolism (glycolysis) into intermediates • Oxidative (mitochondrial) breakdown of intermediates into CO2, water, and ATP

22. Stage 1 Digestion in GI tract lumen to absorbable forms. Transport via blood to tissue cells. PROTEINS CARBOHYDRATES FATS Glucose and other sugars Fatty acids Amino acids Glycerol Stage 2 Anabolism (incorporation into molecules) and catabolism of nutrients to form intermediates within tissue cells. Glycogen Glucose Proteins Fats NH3 Pyruvic acid Acetyl CoA Stage 3 Oxidative breakdown of products of stage 2 in mitochondria of tissue cells. CO2 is liberated, and H atoms removed are ultimately delivered to molecular oxygen, forming water. Some energy released is used to form ATP. Krebs cycle Infrequent CO2 O2 Oxidative phosphorylation (in electron transport chain) H2O H Catabolic reactions Anabolic reactions Figure 24.3

23. Oxidation-Reduction (Redox) Reactions • Oxidation; gain of oxygen or loss of hydrogen • Oxidation-reduction (redox) reactions • Oxidized substances lose electrons and energy • Reduced substances gain electrons and energy

24. Oxidation-Reduction (Redox) Reactions • Coenzymes act as hydrogen (or electron) acceptors • Nicotinamide adenine dinucleotide (NAD+) • Flavin adenine dinucleotide (FAD)

25. Loss of hydrogen atoms (oxidation) C6H12O6 6 CO2 Energy 6 O2 + 6 H2O + + Glucose (ATP) Gain of hydrogen atoms (reduction) 0 When glucose is converted to carbon dioxide • It loses hydrogen atoms, which are added to oxygen, producing water Figure 6.5A

26. Loss of hydrogen atoms (oxidation) C6H12O6 6 CO2 Energy 6 O2 + 6 H2O + + Glucose (ATP) Gain of hydrogen atoms (reduction) 0 • Glucose loses hydrogen atoms = oxidization (oxidation is loss) • Oxygen gains hydrogen atoms = reduction (reduction is gain) • “OIL RIG” Figure 6.5A

27. ATP Synthesis • Two mechanisms • Substrate-level phosphorylation • Oxidative phosphorylation

28. Substrate-Level Phosphorylation • High-energy phosphate groups directly transferred from phosphorylated substrates to ADP • Occurs in glycolysis and the Krebs cycle

29. Catalysis Enzyme Enzyme (a) Substrate-level phosphorylation Figure 24.4a

30. Oxidative Phosphorylation • Chemiosmotic process • Couples the movement of substances across a membrane to chemical reactions

31. Oxidative Phosphorylation • In the mitochondria • Carried out by electron transport proteins • Nutrient energy is used to create H+ gradient across mitochondrial membrane • H+ flows through ATP synthase • Energy is captured and attaches phosphate groups to ADP

33. High H+ concentration in intermembrane space Membrane Proton pumps (electron transport chain) ATP synthase Energy from food ADP + Low H+ concentration in mitochondrial matrix (b) Oxidative phosphorylation Figure 24.4b

34. Carbohydrate Metabolism • Oxidation of glucose C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat • Glucose is catabolized in three pathways • Glycolysis • Krebs cycle • Electron transport chain and oxidative phosphorylation

35. Chemical energy (high-energy electrons) Chemical energy Electron transport chain and oxidative phosphorylation Glycolysis Krebs cycle Pyruvic acid Glucose Mitochondrial cristae Mitochondrion Cytosol Via oxidative phosphorylation Via substrate-level phosphorylation 1 2 3 During glycolysis, each glucose molecule is broken down into two molecules of pyruvic acid in the cytosol. The pyruvic acid then enters the mitochondrial matrix, where the Krebs cycle decomposes it to CO2. During glycolysis and the Krebs cycle, small amounts of ATP are formed by substrate- level phosphorylation. Energy-rich electrons picked up by coenzymes are transferred to the elec- tron transport chain, built into the cristae membrane. The electron transport chain carries out oxidative phosphorylation, which accounts for most of the ATP generated by cellular respiration. Figure 24.5

36. Thank you

37. Video:

38. Oxidation-reduction reactions involve the loss and gain of electrons. The reactant oxidized will lose electrons, while the reactant reduced will gain electrons. In biological oxidation-reduction reactions the loss and gain of electrons is often associated with the loss and gain of hydrogen atoms. Electrons are still being transferred since the hydrogen atom contains an electron.

39. Glycolysis • 10-step pathway • Anaerobic • Occurs in the cytosol • Glucose  2 pyruvic acid molecules • Three major phases • Sugar activation • Sugar cleavage • Sugar oxidation and ATP formation

40. Phases of Glycolysis • Sugar activation • Glucose is phosphorylated by 2 ATP to form fructose-1,6-bisphosphate

41. Phases of Glycolysis • Sugar cleavage • Fructose-1,6-bisphosphate is split into 3-carbon sugars • Dihydroxyacetone phosphate • Glyceraldehyde 3-phosphate

42. Phases of Glycolysis • Sugar oxidation and ATP formation • 3-carbon sugars are oxidized (reducing NAD+) • Inorganic phosphate groups (Pi) are attached to each oxidized fragment • 4 ATP are formed by substrate-level phosphorylation

43. Electron trans- port chain and oxidative phosphorylation Glycolysis Krebs cycle Carbon atom Phosphate Glucose Phase 1 Sugar Activation Glucose is activated by phosphorylation and converted to fructose-1, 6-bisphosphate 2 ADP Fructose-1,6- bisphosphate Figure 24.6 (1 of 3)

44. Electron trans- port chain and oxidative phosphorylation Glycolysis Krebs cycle Carbon atom Phosphate Fructose-1,6- bisphosphate Phase 2 Sugar Cleavage Fructose-1, 6-bisphosphate is cleaved into two 3-carbon fragments Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Figure 24.6 (2 of 3)

45. Electron trans- port chain and oxidative phosphorylation Glycolysis Krebs cycle Carbon atom Phosphate Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Phase 3 Sugar oxidation and formation of ATP The 3-carbon frag- ments are oxidized (by removal of hydrogen) and 4 ATP molecules are formed 2 NAD+ 4 ADP 2 NADH+H+ 2 Pyruvic acid NADH+H+ 2 2 NAD+ 2 Lactic acid To Krebs cycle (aerobic pathway) Figure 24.6 (3 of 3)

46. Glycolysis • Final products of glycolysis • 2 pyruvic acid • Converted to lactic acid if O2 not readily available • Enter aerobic pathways if O2 is readily available • 2 NADH + H+ (reduced NAD+) • Net gain of 2 ATP

47. Krebs Cycle • Occurs in mitochondrial matrix • Fueled by pyruvic acid and fatty acids

48. Krebs Cycle • Transitional phase • Each pyruvic acid is converted to acetyl CoA • Decarboxylation: removal of 1 C to produce acetic acid and CO2 • Oxidation: H+ is removed from acetic acid and picked up by NAD+ • Acetic acid + coenzyme A forms acetyl CoA

49. Krebs Cycle • Coenzyme A shuttles acetic acid to an enzyme of the Krebs cycle • Each acetic acid is decarboxylated and oxidized, generating: • 3 NADH + H+ • 1 FADH2 • 2 CO2 • 1 ATP

50. Krebs Cycle • Does not directly use O2 • Breakdown products of fats and proteins can also enter the cycle • Cycle intermediates may be used as building materials for anabolic reactions PLAY Animation: Krebs Cycle