General, Organic, and Biochemistry, 7e

1. General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

2. Chapter 27 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

3. Glycolysis • Glycolysis:a series of 10 enzyme-catalyzed reactions by which glucose is oxidized to two molecules of pyruvate • there is net conversion of 2ADP to 2ATP

4. Glycolysis - Rexn 1 • reaction 1:phosphorylation of -D-glucose

5. Glycolysis - Rexn 2 • reaction 2:isomerization of glucose 6-phosphate to fructose 6-phosphate

6. Glycolysis - Rexn 2 • this isomerization is most easily seen by considering the open-chain forms of each monosaccharide; it is one keto-enol tautomerism followed by another

7. Glycolysis - Rexn 3 • reaction 3: phosphorylation of fructose 6-phosphate

8. Glycolysis - Rexn 4 • reaction 4:cleavage of fructose 1,6-bisphosphate to two triose phosphates

9. Glycolysis - Rexn 5 • reaction 5: isomerization of triose phosphates • catalyzed by phosphotriose isomerase • reaction involves two successive keto-enol tautomerizations • only the D enantiomer of glyceraldehyde 3-phosphate is formed

10. Glycolysis - Rexn 6 • Reaction 6: oxidation of the -CHO group of D-glyceraldehyde 3-phosphate • the product contains a phosphate ester and a high-energy mixed carboxylic-phosphoric anhydride

11. Glycolysis - Rexn 7 • Reaction 7: transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP

12. Glycolysis - Rexn 8 & 9 • Reaction 8: isomerization of 3-phosphoglycerate to 2-phosphoglycerate • Reaction 9: dehydration of 2-phosphoglycerate

13. Glycolysis - Rexn 10 • Reaction 10: phosphate transfer to ADP

14. Glycolysis • Summing these 10 reactions gives the net equation for glycolysis

15. Reactions of Pyruvate • Pyruvate is most commonly metabolized in one of three ways, depending on the type of organism and the presence or absence of O2

16. Reactions of Pyruvate • A key to understanding the biochemical logic behind two of these reactions of pyruvate is to recognize that glycolysis needs a continuing supply of NAD+ • if no oxygen is present to reoxidize NADH to NAD+, then another way must be found to reoxidize it

17. Pyruvate to Lactate • in vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate • lactate dehydrogenase (LDH) is a tetrameric isoenzyme consisting of H and M subunits; H4 predominates in heart muscle, and M4 in skeletal muscle

18. Pyruvate to Lactate • while reduction to lactate allows glycolysis to continue, it increases the concentration of lactate and also of H+ in muscle tissue • when blood lactate reaches about 0.4 mg/100 mL, muscle tissue becomes almost completely exhausted

19. Pyruvate to Ethanol • Yeasts and several other organisms regenerate NAD+ by this two-step pathway • decarboxylation of pyruvate to acetaldehyde • reduction of acetaldehyde to ethanol

20. Pyruvate to Acetyl-CoA • under aerobic conditions, pyruvate undergoes oxidative decarboxylation • the carboxylate group is converted to CO2 • the remaining two carbons are converted to the acetyl group of acetyl CoA

21. Energy Yield of Glycolysis

22. Catabolism of Glycerol • Glycerol enters glycolysis via dihydroxyacetone phosphate

23. Fatty Acids and Energy • Fatty acids in triglycerides are the principal storage form of energy for most organisms • hydrocarbon chains are a highly reduced form of carbon • the energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

24. b-Oxidation • -Oxidation: a series of five enzyme-catalyzed reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid • Reaction 1: the fatty acid is activated by conversion to an acyl CoA; activation is equivalent to the hydrolysis of two high-energy phosphate anhydrides

25. b-Oxidation • Reaction 2: oxidation of the , carbon-carbon single bond to a carbon-carbon double bond

26. b-Oxidation • Reaction 3: hydration of the double bond • Reaction 4: oxidation of the 2°alcohol to a ketone

27. b-Oxidation • Reaction 5: cleavage of the carbon chain by a molecule of CoA-SH

28. b-Oxidation • this series of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl CoA • b-oxidation of unsaturated fatty acids proceeds in the same way, with an extra step that isomerizes the cis double bond to a trans double bond

29. Energy Yield from b-Oxidation • Yield of ATP per mole of stearic acid (C18)

30. Ketone Bodies • Ketone bodies: acetone, -hydroxybutyrate, and acetoacetate • formed principally in liver mitochondria • can be used as a fuel in most tissues and organs • Formation occurs when the amount of acetyl CoA produced is excessive compared to the amount of oxaloacetate available to react with it • intake high in lipids and low in carbohydrates • diabetes not suitably controlled • starvation

31. Ketone Bodies

32. Protein Catabolism

33. Nitrogen of Amino Acids • -NH2 groups move freely by transamination • pyridoxal phosphate (Section18.7B) forms an imine (a C=N group) with the -amino group of an amino acid • rearrangement gives an isomeric imine • hydrolysis of the isomeric imine gives an -ketoacid and pyridoxamine

34. Nitrogen of Amino Acids • nitrogens to be excreted are collected in glutamate, which is oxidized to a-ketoglutarate and NH4+ • NH4+ then enters the urea cycle

35. The Urea Cycle - Overview • Urea cycle: a cyclic pathway that produces urea from CO2 and NH4+

36. The Urea Cycle

37. The Urea Cycle

38. Amino Acid Catabolism • The breakdown of amino acid carbon skeletons follows two pathways • glucogenic amino acids: ones whose carbon skeletons are degraded to pyruvate or oxaloacetate, both of which may then be converted to glucose by gluconeogenesis • ketogenic amino acids: ones whose carbon skeletons are degraded to acetyl CoA or acetoacetyl CoA, both of which may then be converted to ketone bodies

39. Amino Acid Catabolism

40. Heme Catabolism • When red blood cells are destroyed • globin is hydrolyzed to amino acids • iron is preserved in ferritin, an iron-carrying protein, and reused • heme is converted to bilirubin • bilirubin enters the liver via the bloodstream and is then transferred to the gallbladder where it is stored in the bile and finally excreted in the feces

41. Catabolic Pathways End Chapter 27