Pyruvatdehydrogenaskomplexet

Pyruvate dehydrogenase complex (PDHc) is a mitochondrial multi-enzyme complex that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, providing a critical link between glycolysis and the citric acid cycle. The reaction also generates NADH and carbon dioxide, producing acetyl-CoA for entry into the tricarboxylic acid cycle and, indirectly, for fatty acid synthesis when needed.

The complex consists of three catalytic components: E1 (pyruvate dehydrogenase) responsible for decarboxylation, E2 (dihydrolipoyl transacetylase) that transfers the acetyl group to coenzyme A, and E3 (dihydrolipoamide dehydrogenase) that reoxidizes lipoamide and transfers electrons to NAD+. A lipoamide-containing arm on E2 shuttles intermediates between active sites, and the E3 subunit completes electron transfer to NAD+. The E1 component uses thiamine pyrophosphate as a cofactor, while FAD and NAD+ are involved in the redox steps.

Regulation of PDHc is essential for metabolic control. The activity of the E1α subunit is regulated by phosphorylation: PDH kinases (PDK1–4) inactivate the complex, and PDH phosphatases (PDP1, PDP2) reactivate it in response to cellular signals such as calcium. Allosteric factors also influence activity: high levels of NADH, acetyl-CoA, or ATP inhibit PDHc, whereas pyruvate and ADP can promote activation when energy is needed.

Defects in PDHc or its regulation can lead to metabolic disorders, including lactic acidosis and neurodevelopmental problems. Treatments may include ketogenic diets or thiamine supplementation in certain cases, and management of metabolic crises is essential for affected individuals.