The Multiple Fate of Pyruvate

Dr Imran Siddiqui (MBBS, MPhil)College of Medicine

King Saud Bin Abdulaziz University for Health Sciences

Coenzymes are Needed for the Further Metabolism of Pyruvate

• Which ones, and why??

The Anaerobic NecessityThe Anaerobic Necessity

The production of pyruvate from glucose requires the use of NAD+ Under anaerobic conditions, the resulting NADH cannot be oxidized by respirationThus, other mechanisms must be employed to regenerate NAD+, if energy production from glycolysis is to continue

Catabolic Fates of Pyruvate

From Pyruvate to Acetyl-CoA

• Conversion from a 3-carbon unit to a 2-carbon unit is achieved by

• Oxidative decarboxylation of pyruvate by• The pyruvate dehydrogenase complex, • A cluster of 3 enzymes that • Requires 5 cofactors (4 of which are

vitamin-derived)

Carboxylation Of Pyruvate to Oxaloacetate

• It is a biotin dependent reaction

• It provides the substrate for TCA cycle Gluconeogenesis

The TCA CyclePyruvate Carboxylase

• Pyruvate – can be converted to four (4) different metabolites in one step = at a metabolic crossroads.– Lactate – by lactate dehydrogenase.– Alanine – alanine aminotransferase.– Acetyl CoA - pyruvate dehydrogenase.– Oxaloacetate – pyruvate carboxylase.

• Pyruvate can also be routed toward:– Gluconeogenesis.– Free fatty acid synthesis.– TCA cycle for production of high energy P.