Citric acid cycle
Takes place in mitochondrial matrix.
Stages of citric acid cycle
Pyruvate (3C)
[Pyruvate dehydrogenase complex]
---> Acetyl-CoA (2C)
* +1 x CO2
* +1 x NADH+H
Then, acetyl-CoA (2C)
+ Oxaloacetate (4C)
[Citrate synthase]
---> citrate (6C)
* -1 x H2O
[Aconitase]
---> isocitrate (6C)
[Isocitrate dehydrogenase]
---> alpha-ketoglutarate (5C)
* +1 x CO2
* +1 x NADH+H+
[alpha-ketoglutarate dehydrogenase complex]
---> succinyl-CoA (4C)
* +1 x CO2
* +1 x NADH+H+
[Succinate thiokinase]
---> succinate
* +1 x ATP/GTP
[Succinate dehydrogenase]
---> fumarate
* +1 x FADH2
[Fumarase]
---> malate
* -1 x H2O
[Malate dehydrogenase]
---> oxaloacetate
* +1 x NADH+H+
Overall effect of citric acid cycle
Every turn, one Acetyl-CoA is used and oxaloacetate is regenerated.
Produced:
- 3 x NADH+H+ (from the cycle)
- 1 x NADH+H+ (from pyruvate to acetyl-CoA)
- 1 x FADH2
- 1 ATP/GTP
- 2 CO2 (from the cycle)
- 1 CO2 (from pyruvate to acetyl-CoA)
Other notes on citric cycle
Acetyl-CoA
- Conversion of pyruvate to acetyl-CoA is irreversible
- No pathway available for CoA to be converted back.
- Fatty acids are converted into acetyl-CoA
-> cannot be converted to glucose
- Glycerol (from triglycerol breakdown) can be converted into glucose but is quantitatively unimportant
Succinate thiokinase
(converts succinyl-CoA to succinate)
- There are 2 isoenzymes
- In all tissues, one isoenzyme produces ATP
- In tissues capable of gluconeogenesis (i.e. liver, kidney), the other isoenzyme can produce GTP.
- GTP so generated is used in decarboxylation of oxaloacetate to phosphoenolpyruvate (part of gluconeogensis).
Dehydrogenase complex
Pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex are quite similar.
Both require as cofactors:
- Thiamine diphosphate
- Coenzyme A
- FAD
- NAD
- Lipoate
Role of vitamin in citric cycle
4 of the B vitamins are essential.
- Riboflavin (in FAD)
- Niacin (in NAD)
- Thiamin (Vit B1) (in dehydrogenase complex)
- Pantothenic acid (part of CoA)
