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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 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 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.