1. The TCA Cycle A common metabolic pathway for glucose, aa and fatty acid
Citric Acid Cycle, Krebs Cycle
Pyruvate (actually acetate) from glycolysis is degraded to CO2
Some ATP is produced
More NADH is made
NADH goes on to make more ATP in electron transport and oxidative phosphorylation

5. Entry into the TCA Cycle
Pyruvate Dehydrogenase Complex
Pyruvate is oxidatively decarboxylated to form acetyl-CoA
Pyruvate dehydrogenase uses TPP, CoASH, lipoic acid, FAD and NAD+
Pyruvate dehydrogenase (E1) (丙酮酸脱氢酶)
Dihydrolipoyl transacetylase (E2) (二氢硫辛酰转乙酰基酶)
Dihydrolipoyl dehydrogenase (E3) (二氢硫辛酰脱氢酶)

6. Pyruvate Dehydrogenase Complex
Pyruvate Acetyl-CoA
Pyruvate Dehydrogenase Complex

9. Pyruvate dehydrogenase complex consists of three enzymes

10. Arsenic Compounds Are Poisonous in part because They Sequester Lipoamide

13. ① Condensation

16. Citrate Synthase Formation of citrate
Another example for the induced fit model
OAA, the first substrate to bind to the enzyme, induce a large conformational change, creating a binding site for the second substrate, acetyl-CoA. When citroyl-CoA forms on the enzyme surface, another conformational change brings the side of a crucial Asp residue into position to cleavage the thioester.
This mechanism decreases the likelihood of premature and unproductive cleavage of the thioester bond of acetyl-CoA

19. Aconitase Isomerization of Citrate to Isocitrate
Citrate is a poor substrate for oxidation
So aconitase isomerizes citrate to yield isocitrate which has a secondary -OH, which can be oxidized
Note the stereochemistry of the Rxn: aconitase removes the pro-R H of the pro-R arm of citrate!
Aconitase uses an iron-sulfur cluster

20. ② Dehydration and hygration

25. Isocitrate Dehydrogenase
Oxidative decarboxylation of isocitrate to yield  -ketoglutarate
Classic NAD+ chemistry (hydride removal) followed by a decarboxylation
Isocitrate dehydrogenase is a link to the electron transport pathway because it makes NADH
Know the mechanism!

26. ③ Oxidative decarboxylation

27. ③ Oxidative decarboxylation

28.  -Ketoglutarate Dehydrogenase Complex
A second oxidative decarboxylation
This enzyme is nearly identical to pyruvate dehydrogenase - structurally and mechanistically
Five coenzymes used - TPP, CoASH, Lipoic acid, NAD+, FAD
You know the mechanism if you remember pyruvate dehydrogenase
Another target for arsenic compounds

29. ④ Oxidative decarboxylation

30. Succinyl-CoA Synthetase
A substrate-level phosphorylation
A nucleoside triphosphate is made
Its synthesis is driven by hydrolysis of a CoA ester
The mechanism involves a phosphohistidine

33. Succinate Dehydrogenase
An oxidation involving FAD
This enzyme is actually part of the electron transport pathway in the inner mitochondrial membrane
The electrons transferred from succinate to FAD (to form FADH2) are passed directly to ubiquinone (UQ) in the electron transport pathway

35. Fumarase Hydration across the double bond
trans-addition of the elements of water across the double bond
The actual mechanism is not known for certain

38. Malate Dehydrogenase An NAD+-dependent oxidation
The carbon that gets oxidized is the one that received the -OH in the previous reaction
This reaction is energetically expensive
Go' = +30 kJ/mol
This and the previous two reactions form a reaction triad that we will see over and over!

41. The Fate of Carbon in TCA
Carboxyl C of acetate turns to CO2 only in the second turn of the cycle (following entry of acetate)
Methyl C of acetate survives two cycles completely, but half of what's left exits the cycle on each turn after that.

42. TCA Cycle Summary Total rxn:
Acetyl-CoA+3NAD＋+FAD+GDP+Pi+2H2O→2CO2+3NADH+FADH2+GTP+2H＋+CoA
One Acetyl-CoA through the cycle produces two CO2, one ATP, four reduced coenzymes
Two H2Os are used as substrates
Absolutely depends on O2

43. Function of the TCA Cycle
Produces More ATPs
As a source of biosynthetic precursors
A common final metabolic pathway for glucose, aas and fatty acids
Some Immediates act as effectors to regulate other metabolic pathways
Produces CO2

49. The Glyoxylate Cycle A variant of TCA for plants and bacteria
Acetate-based growth - net synthesis of carbohydrates and other intermediates from acetate - is not possible with TCA
Glyoxylate cycle offers a solution for plants and some bacteria and algae
The CO2-evolving steps are bypassed and an extra acetate is utilized
Isocitrate lyase and malate synthase are the short-circuiting enzymes

50. Glyoxylate Cycle II Isocitrate lyase produces glyoxylate and succinate
Malate synthase does a Claisen condensation of acetyl-CoA and the aldehyde group of glyoxylate - classic CoA chemistry!
The glyoxylate cycle helps plants grow in the dark!
Glyoxysomes borrow three reactions from mitochondria: succinate to oxaloacetate