1. Chapter 20 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

2. Convergence of Pathways
Figure Convergence of the specific pathways of carbohydrate, fat, and protein catabolism into the common pathway, which is made up of citric acid cycle and oxidative phosphorylation.

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

4. Glycolysis
Reaction 1: Phosphorylation of -D-glucose.

5. Glycolysis
Reaction 2: Isomerization of -D-glucose 6-phosphate to -D-fructose 6-phosphate.

6. Glycolysis
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
Reaction 3: Phosphorylation of fructose 6-phosphate.

8. Glycolysis
Reaction 4: Cleavage of fructose 1,6-bisphosphate to two triose phosphates.

9. Glycolysis Reaction 5: Isomerization of triose phosphates.
Catalyzed by phosphotriose isomerase. The mechanism involves two successive keto-enol tautomerizations.
Only the D enantiomer of glyceraldehyde 3-phosphate is formed.

10. Glycolysis
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
Reaction 7: Transfer of a phosphate group from 1,3- bisphosphoglycerate to ADP.

12. Glycolysis
Reaction 8: Isomerization of 3-phosphoglycerate to 2-phosphoglycerate.
Reaction 9: Dehydration of 2-phosphoglycerate.

13. Glycolysis
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.

17. Pyruvate to Lactate
In vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate. Pyruvate, the oxidizing agent, is reduced to lactate.
Lactate dehydrogenase (LDH) is a tetrameric isoenzyme consisting of H and M subunits; H4 predominates in heart muscle, 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.
Acetaldehyde is then reduced to ethanol. NADH is the reducing agent. Acetaldehyde is reduced and is the oxidizing agent in this redox reaction.

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.
This reaction provides entrance to the citric acid cycle.

21. Pentose Phosphate Pathway
Figure Simplified schematic representation of the pentose phosphate pathway, also called a shunt.

22. Energy Yield in Glycolysis

23. Catabolism of Glycerol
Glycerol enters glycolysis via dihydroxyacetone phosphate.

24. 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.

25. -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.

26. -Oxidation
Reaction 2: Oxidation by FAD of the , carbon-carbon single bond to a carbon-carbon double bond.

27. -Oxidation
Reaction 3: Hydration of the C=C double bond to give a 2° alcohol.
Reaction 4: Oxidation of the 2°alcohol to a ketone.

28. -Oxidation
Reaction 5: Cleavage of the carbon chain by a molecule of CoA-SH.

29. -Oxidation
This cycle 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.

30. Energy Yield on -Oxidation
Yield of ATP per mole of stearic acid (C18).

31. Ketone Bodies
Ketone bodies: Acetone, -hydroxybutyrate, and acetoacetate;
Are 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 and take it into the TCA; for example:
Dietary intake is high in lipids and low in carbohydrates.
Diabetes is not suitably controlled.
Starvation.

32. Ketone Bodies

33. Protein Catabolism
Figure Overview of pathways in protein catabolism.

34. Nitrogen of Amino Acids
-NH2 groups move freely by transamination
Pyridoxal phosphate forms an imine (a C=N group) with the -amino group of an amino acid.
Rearrangement of the imine gives an isomeric imine.
Hydrolysis of the isomeric imine gives an -ketoacid and pyridoxamine. Pyridoxamine then transfers the NH2 group to another a-ketoacid.

35. Nitrogen of Amino Acids
Nitrogens to be excreted are collected in glutamate, which is oxidized to a-ketoglutarate and NH4+.
The conversion of glutamate to -ketoglutarate is an example of oxidative deamination.
NH4+ then enters the urea cycle.

36. Urea Cycle—An Overview
Urea cycle: A cyclic pathway that produces urea from CO2 and NH4+.

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

38. Amino Acid Catabolism
Figure Catabolism of the carbon skeletons of amino acids.

39. Amino Acid Catabolism

40. Heme Catabolism When red blood cells are destroyed:
Globin is hydrolyzed to amino acids to be reused.
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. Heme Catabolism
Figure Heme degradation from heme to biliverdin to bilirubin.

42. Heme Catabolism
Figure A summary of catabolism showing the role of the common metabolic pathway.