to keep these pictures clearer the involvment of specific amino acid sidechains are not shown - rest assured that nothing happens without the enzyme

CO2 enters the active site as HCO3-. This is essential since it must be in this form to attach the terminal phosphate of ATP

The results of the previous step is shown - ADP is formed as well as the mixed anhydride between carbonate and phophate. This is an "activated form of CO2. ADP leaves the active site

The results of the previous step is shown - The nitrogen of the biotin (covalently bound to the enzyme via a Lysine sidechain) attacks the carbonate "side" of the mixed anhydride

The results of the previous step is shown - a stable carboxybiotin intermediate is formed.
Phsophate leaves the active site

The results of the previous step is shown - pyruvate enters the active site.
The required metal ion cofactor (now shown) initiates the aldol reaction by pulling on the ketone of pyruvate

The results of the previous step is shown - The pyruvate is in the ENol transition state. THe electrons from the Enol move back and one pair of electrons from the C=C double bond attacks the carboxy group of the biotin

The results of the previous step is shown - Oxaloacetate has formed and biotin is back to its original state

Anaerobic Glucose Metabolism

Pyruvate Carboxylase Information


Enzyme Name

Pyruvate Carboxylase


Reaction Catalyzed

Addition of CO2 to C3 of pyruvate via an Aldol Reaction

Reaction Type

Pyruvate adds "C" via an Aldol Reaction. There are two group transfer reactions to prepare CO2 for this process

Pathway Involvement

Gluconeogenesis ONLY

This enzyme is the first of two that are required to bypass the pyruvate kinase reaction of glycolysis. Note that pyruvate kinase has a ΔGo' that so favors glycolysis that it is unlikely that is could be driven backwards. Therefore two ATP (or ATP equivalent) dependent reactions:

  1. pyruvate carboxylase
  2. PEP carboxykinase
are required to get from pyruvate back to phosphoenolpyruvate.

Cofactors/Cosubstrates

Biotin is required and is covalently bound to the enzyme
A Mn2+ ion is also required for initiation of the aldol reaction.
CO2 and ATP are cosubstrates, while ADP and PO4= are coproducts