Question

Why does acetyl CoA, a product of fatty acid catabolism, influence the pyruvate dehydrogenase complex (PDH), a control point in carbohydrate catabolism?

When fatty acid breakdown is high, ADP is low and PDH is inhibited by phosphatase activity.
When fatty acid breakdown is inhibited, PDH is inhibited by acetyl CoA due to phosphatase activity.
When fatty acid breakdown is high, NADH levels drop, causing an increase in E2 activity.
When fatty acid breakdown is high, PDH is inhibited by acetyl CoA due to pyruvate kinase activity.
When fatty acid breakdown is inhibited, ADP is low, causing a decrease in activity.

Answer 1

Answer : Option A

When fatty acid breakdown is high, ADP is low and PDH is inhibited by phosphatase activity.

The entry point of pyruvate into the TCA cycle is regulated by pyruvate dehydrogenase complex. This complex is in turn regulated by allosteric and covalent modification of the pyruvate dehydrogenase (PDH) component of the complex. The final products of the overall reaction (NADH and acetyl-CoA) are known to be potent allosteric inhibitors of PDH. Simply put, when the levels of acetyl-CoA, ATP and NADH are high, the oxidation of pyruvate to acetyl-CoA is markedly decreased. When fatty acid breakdown occurs, it provides all three metabolites (acetyl-CoA, ATP and NADH) and thus decreases the need for pyruvate oxidation.

PDH activity is regulated by ‘phosphorylation state’. PDH is most active in the dephosphorylated state. Phosphorylation of PDH is catalysed by four specific PDH kinases known as PDK1, PDK2, PDK3, and PDK4. The activity of these kinases is enhanced when cellular energy charge is high which is reflected by an increase in the level of ATP, NADH and acetyl-CoA. So we can infer that, when levels of ATP, NADH and acetyl-CoA are high, kinases are active and these active kinases cause phosphorylation of PDH, thus converting it into inactive form.

On the other hand, an increase in pyruvate strongly inhibits PDH kinases. PDH kinases are also regulated by ADP, NAD⁺ and CoASH. Their levels increase when energy levels fall.