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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
?and why? • Which ones,
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.