Cytosolic oxaloacetate decarboxylation in gluconeogenesis

OAA is decarboxylated and phosphorylated to PEP in the cytosol by PEPCK. The reaction is driven by hydrolysis of guanosine triphosphate ([GTP] see Fig. 1). The combined actions of PC and PEPCK provide an energetically favorable pathway from pyruvate to PEP. PEP is then acted on by the reactions of glycolysis running in the reverse direction until it becomes fructose 1,6-bisphosphate.

Figure 1: PEP synthesis in the cytosol. [Note: The process moves nicotinamide adenine dinucleotide (NADH) reducing equivalents required for gluconeogenesis out of mitochondria into the cytosol.] MDm and MDc =mitochondrial and cytosolic isozymes of malate dehydrogenase; GTP and GDP = guanosine tri- and diphosphates; ADP = adenosine diphosphate.

The pairing of carboxylation with decarboxylation drives reactions that would otherwise be energetically unfavorable. This strategy is also used in fatty acid (FA) synthesis .