5.2 The citric acid cycle
With the conversion of pyruvate to acetyl-CoA, the carbon derived from glucose has reached a central hub of energy metabolism; degradation of all nutrients—carbohydrates, amino acids, and fat—proceeds through this stage. The next step toward complete oxidation is the citric acid cycle (or tricarboxylic acid cycle, TCA). Its basic idea consists in releasing the carbon as CO2, and retaining the hydrogen for 'cold combustion' in the respiratory chain. However, if we look more closely, we see that the this description is not quite sufficient. For the sake of simplicity, let us formally (not actually) prematurely get rid of the coenzyme A and convert acetyl-CoA to acetate:
CH3CO-S-CoA + H2O → CH3COOH + CoA-SH
If we look back at figure Figure 5-1, we see that the TCA produces 4 molecules of H2 and two molecules of CO2. Now, if we attempt to balance the acetate with these amounts of CO2 and H2:
CH3COOH → 2 CO2 + 4 H2
we see that we are short 4 hydrogens and 2 oxygens on the left side. However, we can balance the equation if we add two molecules of water:
CH3COOH + 2 H2O → 2 CO2 + 4 H2
Therefore, half of the hydrogen produced in the TCA is gained by the reduction of water; the water-derived oxygen is used to complete the oxidation of the acetyl carbon. Hydrogen derived both from water and the acetyl group is then re-oxidized in the respiratory chain to generate ATP.
The energy yield of the TCA itself, in terms of directly generated enery-rich phosphoanhydride bonds, is very modest—just one molecule of GTP, which is equivalent to ATP, is generated per molecule of acetyl-CoA degraded, compared to approximately 30 in the respiratory chain. It is clear therefore that the TCA's main contribution to ATP generation is to provide H2 for the respiratory chain.