7.1 Reactions in gluconeogenesis

Gluconeogenesis converts pyruvate and oxaloacetate to glucose. It is essentially a reversal of glycolysis, with workarounds for those reactions of glycolysis that are energetically irreversible. These four reactions are highlighted in Figure 7-1.

The final reaction of glycolysis is the transfer of the phosphate group from phosphoenolpyruvate (PEP) to ATP. This reaction is irreversible because of the strongly exergonic nature of the accompanying rearrangement of pyruvate from the enol to the keto form (cf. section 3.4.4). In gluconeogenesis, it takes two enzymatic steps to turn pyruvate back into PEP:

Carboxylation to oxaloacetate by pyruvate carboxylase (Figure 7.1-1), and
Conversion of the latter to PEP by phosphoenolpyruvate carboxykinase (Figure 7.1-2a).

Pyruvate carboxylase requires biotin as a coenzyme. This coenzyme is flexibly attached to the enzyme (Figure 7.1-1a) in a manner reminiscent of lipoic acid in pyruvate dehydrogenase (cf. Figure 5.1-1), and for a similar reason: The reaction occurs in separate steps at different active sites, which with some biotin-dependent enzymes (though not with pyruvate carboxylase) are located on separate enzyme subunits.

Biotin serves as an intermediate carrier of a carboxyl group that is generated from bicarbonate, which is equivalent to CO₂. Remarkably, therefore, we are able to metabolically fix CO₂, just like plants! Before you try to claim Kyoto treaty credits for this ability, however, it is necessary to consider that the very same molecule of CO₂ gets released again in the very next step. The whole purpose of attaching it consists in the facilitation of the subsequent reaction, which is outlined in Figure 7.1-2a.