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.

1. Riboflavin (in FAD)
2. Niacin (in NAD)
3. Thiamin (Vit B1) (in dehydrogenase complex)
4. Pantothenic acid (part of CoA)