PDHkompleksi

PDHkompleksi, or the pyruvate dehydrogenase complex, is a mitochondrial multi-enzyme assembly that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, providing the acetyl group that enters the citric acid cycle. It thereby links glycolysis in the cytosol to aerobic respiration in mitochondria and plays a central role in cellular energy production.

The complex consists of three catalytic components: E1 (pyruvate dehydrogenase), E2 (dihydrolipoyl transacetylase) and E3 (dihydrolipoamide dehydrogenase). E1 decarboxylates pyruvate and transfers the resulting acetyl group to the lipoamide cofactor on E2. E2 then transfers the acetyl group to coenzyme A, forming acetyl-CoA. E3 reoxidizes the reduced lipoamide, funneling electrons to NAD+, which becomes NADH. The E1 component requires thiamine pyrophosphate (TPP) as a cofactor, and the complex uses lipoic acid, CoA, FAD, and NAD+ as additional cofactors.

Regulation of PDHkompleksi is primarily through reversible phosphorylation. PDH kinase (PDK) inactivates E1 by phosphorylation, while PDH phosphatase (PDP) reactivates it by dephosphorylation. PDK activity rises with high levels of NADH, ATP and acetyl-CoA; PDP is activated by calcium and, in many tissues, by insulin signaling. Pyruvate availability also promotes PDH activity, favoring flux into the citric acid cycle and oxidative metabolism.

Genetic defects in PDHkompleksi or its regulatory enzymes cause pyruvate dehydrogenase deficiency, a metabolic disorder marked by lactic acidosis and neurodevelopmental problems. Treatment options include ketogenic diets and, in select cases, thiamine supplementation or inhibitors of PDK to improve PDH activity.