Bio Chemistry

BIOCHEMISTRY 3(2+1)

Lesson 20 : The Citric Acid Cycle

Role of enzymes involved in the TCA cycle

1. Citrate synthase

Irreversible reaction


Acetyl CoA reacts with oxaloacetate --> citrate and CoA

2. Aconitase

Citrate --> isocitrate

3. Isocitrate dehydrogenase

Irreversible reaction


Substrate first oxidized (2e- and H+ given to NAD+), then decarboxylated


Isocitrate -->?-ketoglutarate + CO2 + NADH + H+

4. ?-ketoglutarate dehydrogenase complex

-ketoglutarate first decarboxylated, oxidized (2e- and H+ given to NAD+), and HS-CoA added

Product is succinyl CoA

Enzyme complex similar the PDH, but has dihydrolipoamide succinyltransferase instead of acetyltransferase.

5. Succinyl CoA synthetase or succinate thiokinase

Succinyl CoA --> succinate


Substrate has high energy thioester bond; that energy is stored as nucleoside triphosphate via substrate level phosphorylation


GDP +Pi --> GTP mammals


ADP +Pi --> ATP plants and bacteria

6. Succinate dehydrogenase complex

Enzyme is embedded in inner mitochondrial membrane.

Has FAD covalently bound to it (prosthetic group).


Converts succinate --> fumarate with generation of FADH2 --> ETS


FAD is regenerated by reduction of a mobile molecule called ubiquinone (coenzyme Q) --> QH2.

7. Fumarase

   fumarate --> malate

8. Malate dehydrogenase

   L-malate --> oxaloacetate

   2e- and H+ given to NAD+ --> NADH