Carbohydrate metabolism

1. Carbohydrate metabolism Chapter 3 (cont.)

2. Break-down of glucose to generate energy - Also known as Respiration. - Comprises of these different processes depending on type of organism: I. Anaerobic Respiration II. Aerobic Respiration

3. Anaerobic Respiration Comprises of these stages: glycolysis: glucose 2 pyruvate + NADH fermentation: pyruvate lactic acid or ethanol cellular respiration:

4. Aerobic Respiration Comprises of these stages: • Oxidative decarboxylation of pyruvate • Citric Acid cycle • Oxidative phosphorylation/ Electron Transport Chain(ETC)

5. Brief overview of catabolism of glucose to generate energy STARCHY FOOD α – AMYLASE ; MALTASES Glucose Glucose converted to glu-6-PO4 Start of cycle Glycolysis in cytosol Cycle : anaerobic Aerobic condition; in mitochondria 2[Pyruvate+ATP+NADH] Pyruvate enters as AcetylcoA Anaerobiccondition - Krebs Cycle - E transport chain Lactic Acid fermentation in muscle. Only in yeast/bacteria Anaerobic respiration or Alcohol fermentation

6. Gluconeogenesis • Conversion of pyruvate to glucose • Biosynthesis and the degradation of many important biomolecules follow different pathways • There are three irreversible steps in glycolysis and the differences bet. glycolysis and gluconeogenesis are found in these reactions • Different pathway, reactions and enzyme STEP 1 p.495

7. is the biosynthesis of new glucose from non-CHO precursors. • this glucose is as a fuel source by the brain, testes, erythrocytes and kidney medulla • comprises of 9steps and occurs in liver and kidney • the process occurs when quantity of glycogen have been depleted - Used to maintain blood glucose levels. • Designed to make sure blood glucose levels are high enough to meet the demands of brain and muscle (cannot do gluconeogenesis). • promotes by low blood glucose level and high ATP • inhibits by low ATP • occurs when [glu] is low or during periods of fasting/starvation, or intense exercise • pathway is highly endergonic *endergonic is energy consuming

8. STEP 2

9. The oxalocetate formed in the mitochondria have two fates: - continue to form PEP - turned into malate by malate dehydrogenase and leave the mitochondria, have a reaction reverse by cytosolic malate dehydrogenase • Reason?

11. as • Controlling glucose metabolism • found in Cori cycle • shows the cycling of glucose due to gycolysis in muscle and gluconeogenesis in liver • This two metabolic pathways are not active simultaneously. • when the cell needs ATP, glycolisys is more active • When there is little need for ATP, gluconeogenesis is more active As energy store for next exercise Fig. 18-12, p.502

12. Cori cycle requires the net hydrolysis of two ATP and two GTP.

13. Fig. 18-13, p.503

14. The Citric Acid cycle • Cycle where 30 to 32 molecules of ATP can be produced from glucose in complete aerobic oxidation • Amphibolic – play roles in both catabolism and anabolism • The other name of citric acid cycle: Krebs cycle and tricarboxylic acid cycle (TCA) • Takes place in mitochondria

15. Fig. 19-2, p.513

17. Steps 3,4,6 and 8 – oxidation reactions Fig. 19-3b, p.514

18. 5 enzymes make up the pyruvate dehydrogenase complex: • pyruvate dehydrogenase (PDH) • Dihydrolipoyl transacetylase • Dihydrolipoyl dehydrogenase • Pyruvate dehydrogenase kinase • Pyruvate dehydrogenase phosphatase Conversion of pyruvate to acetyl-CoA

19. Step 1 Formation of citrate p.518

20. Step 2 Isomerization Table 19-1, p.518

21. cis-Aconitate as an intermediate in the conversion of citrate to isocitrate Fig. 19-6, p.519

23. Step 3 Formation of α-ketoglutarate and CO2 – first oxidation Fig. 19-7, p.521

24. Step 4 Formation of succinyl-CoA and CO2 – 2nd oxidation p.521

25. Step 5 Formation of succinate p.522

26. Step 6 Formation of fumarate – FAD-linked oxidation p.523a

27. Step 7 Formation of L-malate p.524a

28. Regeneration of oxaloacetate – final oxidation step Step 8 p.524b

29. Krebs cycle produced: • 6 CO2 • 2 ATP • 6 NADH • 2 FADH2 Fig. 19-8, p.526

30. Table 19-3, p.527

31. Fig. 19-10, p.530

32. Fig. 19-11, p.531

33. Fig. 19-12, p.533

34. Fig. 19-15, p.535

35. Overall production from glycolysis, oxidative decarboxylation and TCA: Electron transportation system

36. Glycogen metabolism Fig. 18-CO, p.487

37. Glycogen stored in muscle and liver cells. • Important in maintaining blood glucose levels. • Glycogen structure: α-1,4 glycosidic linkages with α-1,6 branches. • Branches give multiple free ends for quicker breakdown or for more places to add additional units. Fig. 18-1, p.488

38. STEP 1 Glycogen phosphorylase STEP 2 Phosphoglucomutase

39. Fig. 18-2, p.489

40. Glycogen Synthesis • Not reverse of glycogen degradation because different enzymes are used. • About 2/3 of glucose ingested during a meal is converted to glycogen. • First step is the first step of glycolysis: • hexokinase • glucose --------------> glucose 6-phosphate • There are three enzyme-catalyzed reactions: • phosphoglucomutase • glucose 6-phosphate ---------------------> glucose 1-phosphate • glucose 1-phosphate ---------------> UDP-glucose (activated form of glucose) • glycogen synthase • UDP-glucose ----------------------> glycogen • Glycogen synthase cannot initiate glycogen synthesis; requires preexisting primer of glycogen consisting of 4-8 glucose residues with a (1,4) linkage. • Protein called glycogenin serves as anchor; also adds 7-8 glucose residues. • Addition of branches by branching enzyme (amylo-(1,4 --> 1,6)-transglycosylase). • Takes terminal 7 glucose residues from nonreducing end and attaches it via a(1,6) linkage at least 4 glucose units away from nearest branch.

41. p.490

42. Fig. 18-3, p.491

43. Fig. 18-4, p.492

44. REGULATION OF GLYCOGEN METABOLISM • Mobilization and synthesis of glycogen under hormonal control. • Three hormones involved: • 1) Insulin • 51 a.a. protein made by b cells of pancreas. • Secreted when [glucose] high --> increases rate of glucose transport into muscle and fat via GLUT4 glucose transporters. • Stimulates glycogen synthesis in liver. • 2) Glucagon • 29 a.a. protein secreted by a cells of pancreas. • Operational under low [glucose]. • Restores blood sugar levels by stimulating glycogen degradation. • 3) Epinephrine • Stimulates glycogen mobilization to glucose 1-phosphate --> glucose 6-phosphate. • Increases rate of glycolysis in muscle and the amount of glucose in bloodstream.

45. Regulation of glycogen phosphorylase and glycogen synthase • Reciprocal regulation. • Glycogen synthase -P --> inactive form (b). • Glycogen phosphorylase-P ---> active (a). • When blood glucose is low, protein kinase A activated through hormonal action of glucagon --> glycogen synthase inactivated and phosphorylase kinase activated --> activates glycogen phosphorylase --> glycogen degradation occurs. • Phosphorylase kinase also activated by increased [Ca2+] during muscle contraction. • To reverse the same pathway involves protein phosphatases, which remove phosphate groups from proteins --> dephosphorylates phosphorylase kinase and glycogen phosphorylase (both inactivated), but dephosphorylation of glycogen synthase activates this enzyme. • Protein phosphatase-1 activated by insulin --> dephosphorylates glycogen synthase --> glycogen synthesis occurs. • In liver, glycogen phosphorylase a inhibits phosphatase-1 --> no glycogen synthesis can occur. • Glucose binding to protein phosphatase-1 activated protein phosphatase-1 --> it dephosphorylates glycogen phosphorylase --> inactivated --> no glycogen degradation. • Protein phosphatase-1 can also dephosphorylate glycogen synthase --> active.

46. p.493