1. Acetyl-CoA and the Citric Acid Cycle
Dr. Kevin Ahern

2. Respiration Conversion of nutrients into useful energy for the cell
Carbohydrates - Sugars
Proteins - Amino Acids
Fats - Fatty Acids & Glycerol

3. Acetyl-CoA

5. Pyruvate Dehydrogenase
Ethanol
Mitochondrial Enzyme
Very large multimeric complex
Three subunits - E1, E2, E3
NAD+
No O2
CO2
NADH
Pyruvate
Acetaldehyde
NAD+ O2
Animals
Bacteria & Yeast
NAD+
NADH
NADH + CO2
Acetyl-CoA
E1 Subunit of Pyruvate Dehydrogenase

6. NAD+
NADH
Acetaldehyde
Ethanol
Alcohol
Dehydrogenase

7. Pyruvate Dehydrogenase
CO2
TPP-Acetaldehyde
Bacteria / Yeast
Acetaldehyde
(Mostly in low O2)
Electron transfer
to lipoamide-S-S E2
Pyruvate Dehydrogenase
Acetyl-Lipoamide
FAD
FADH2 E3
NAD+
NADH
Acetyl-CoA

8. E2 E1 E3 Acetyl-Lipoamide Acetyl-CoA TPP-Acetaldehyde Pyruvate
Electron transfer
to lipoamide-S-S
Pyruvate E3
Acetyl-CoA

9. Lipoamide Oxidized/Reduced

10. (Favor Dephosphorylation) These ions Activate
PD = Pyruvate Dehydrogenase
Phosphorylation Inactivates
Dephosphorylation Activates
PD Kinase Puts Phosphate on
PD Phosphatase Takes Phosphate off
(Favor Dephosphorylation)
These ions Activate
Be careful not to confuse
PD with the PD Phosphatase
or the PD Kinase
These Hormones Inactivate PD
(Favor Phosphorylation)

11. Acetyl-CoA

13. +
Very Negative
ΔG°’
Citrate
Synthase H +

14. Aconitase

15. First oxidative decarboxylation+
NAD+
Isocitrate
Dehydrogenase +
NADH + CO2
First oxidative decarboxylation

16. + + + + NAD+ CoASH NADH CO2 Second oxidative decarboxylation
α-ketoglutarate
dehydrogenase + +
NADH
CO2
Second oxidative
decarboxylation

17. Phosphorylation in Cycle
+ GDP + Pi
Succinyl-CoA
Synthetase
+ GTP + CoASH
Symmetrical Product
Only Substrate Level
Phosphorylation in Cycle

18. Succinyl-CoA Synthetase Mechanism

19. Third Oxidation of Cycle
+ FAD
Succinate
Dehydrogenase
Third Oxidation of Cycle
+ FADH2

20. Succinate Dehydrogenase
Enzyme is embedded in inner mitochondrial membrane
Only enzyme of Citric Acid Cycle not found in matrix

21. Electron Movement
Reaction

22. + H2O
Fumarase

23. citrate synthase reaction
+ NAD+
Malate
Dehydrogenase
Very positive ΔG°’
Reaction pulled by
citrate synthase reaction
Fourth and final
oxidation of cycle
+ NADH

25. Citric Acid Cycle Summary
Input 2 Carbons (1 Acetyl CoA)
Release 2 CO2 Molecules
Four Oxidations
3 NADH, 1 FADH2, 1 GTP Per Turn of Cycle

26. Each Citric Acid Cycle Intermediate Functions in Other Pathways
Citrate - Glyoxylate Cycle, Allosteric Effector, Shuttle System
Isocitrate - Glyoxylate Cycle
a-Ketoglutarate - Amino Acid/Nitrogen Metabolism
Succinyl-CoA - Heme Synthesis, Amino Acid Metabolism
Succinate - Glyoxylate Metabolism, Odd Chain Fatty Acid Metabolism
Fumarate - Nucleotide Metabolism
Malate - Shuttle System
Oxaloacetate - Gluconeogenesis, Amino Acid Metabolism

27. Anaplerotic / Cataplerotic

29. Arnon-Buchanan Cycle

31. Two per turn
of cycle

32. Isocitrate Lyase
Isocitrate
Succinate + Glyoxylate +

33. Malate Synthase
Acetyl-CoA + Glyoxylate
L-Malate +

34. Glyoxylate Cycle Summary Input 4 Carbons (2-Acetyl CoA)
Releases 0 CO2 Molecules
Produces One Extra Oxaloacetate
Two Oxidations
1 NADH, 1 FADH2 1(extra ) Oxaloacetate Per Turn of Cycle
Net Synthesis of Glucose from Acetyl-CoA
Citric Acid Cycle Summary
Input 2 Carbons (1 Acetyl CoA)
Releases 2 CO2 Molecules
Four Oxidations
3 NADH, 1 FADH2, 1 GTP Per Turn of Cycle
No Net Synthesis of Glucose from Acetyl-CoA

36. The Animals’ Dilemma No net glucose synthesis from fat

37. Ketone Body Metabolism