Phosphoenolpyruvate Carboxykinase Information

Enzyme Name

Phosphoenolpyruvate Carboxykinase

Reaction Catalyzed

Addition of phosphate to pyruvate with comcomitant aldol cleavage of CO₂ from Oxaloacetate

Reaction Type

Concomitant Group Transfer and Aldol Reactions

Pathway Involvement

Gluconeogenesis ONLY

Cofactors/Cosubstrates

a metal ion, usually Mn²⁺, is required as a cofactor

GTP is a cosubstrate and GDP as well as C)₂ are coproducts

Rationale

This is the second half of the two reactions that are required to bypass the pyruvate kinase reaction of glycolysis. This one takes the smae carboxyl group that was just put onto pyruvate by the pyruvate carbolylase enzyme. This uses the Free Energy of generating a CO₂ from and Aldol cleavage to drive the "enol" formation and then the the "enol" attacks GTP for a group transfer reaction.

while the ΔG^o' is not very far from 0, this reaction is virtually irreversible in reality toward product phosphoenolpyruvate. The reason is that CO₂ concentrations are very low in the tissues. We go to great lengths to keep our CO₂ concentration low. There are two mechanisms:

1. In the tissues, where CO₂ is generated and therefore in relatively high concentration, an enzyme called Carbonic Anhydrase (CA) rapdidly converts CO₂ to HCO₃^- + H⁺ by reaction with water in a reversible reaction.
2. In the lungs, where CO₂ concentration is low (atmosphereic concetrations), the same reaction catalyzed by the same enzyme runs the other way to generate CO₂ so that we can exhale it.

A metal ion helps the aldol reaction get started by providing a strong positive charge to start the electron pulling.

ΔG^o'

-2.2 kJ/M

K_eq

Comments

Starting from standard state and allowing the reaction to come to equilibrium the PEP concentration would end up ~2 times higher than the concetration of oxaloacetate.

The Standard Free Energy slightly favors PEP production.

Mechanism for Chemistry

Mechanism for Enzyme

Hover your mouse over a step to reveal a description

PEP Carboxykinase. Animation of the PEPcarboxykinase reaction Blue: represents the enzyme. The Mn²⁺ represents the crucial enzyme active site metal ion. The GTP overlays the Mn because this is a 2D representation of a 3D map. "Start" begins an animation of the reaction series. It proceeds through the reaction in the "forward" direction and then "backwards" again. Note how the enzyme is involved. "+" increases speed while "-" decreases the animation speed. You may also step through the reaction using "next" or "previous"

Notice: how the "positive charge" on the metal ion begins the process of the electron pulling cascade. In a normal aldol cleavage reaction the electron cascade would collapse back towrd the original because of the instability of the enol. In this case, however, the proximity og the GTP allows a different track. The enol actuially attacks the phosphate and a group transfer occurs... generating the final product.

Compare the animated reaction to the "arrow pushing" scheme at the right. See if you can correlate the electron movement in the animation to the arrows in the static picture above.

Picture of Enzyme with substrate