The Multiple Fate Of Pyruvate

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 Necessity

The production of pyruvate from glucose requires the use of NAD+ Under anaerobic conditions, the resulting NADH cannot be oxidized by respiration Thus, 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 2carbon 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 Cycle Pyruvate 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.