pyru-vate (Figure 45–17). A second enzyme, phospho- enolpyruvate carboxykinase, catalyzes the decarboxy- lation and phosphorylation of oxaloacetate to phospho- enolpyruvate using GTP (or ITP) as the phosphate donor. Thus, reversal of the reaction catalyzed by pyru- vate kinase in glycolysis involves two endergonic reac- tions.
In pigeon, chicken, and rabbit liver, phospho- enolpyruvate carboxykinase is a mitochondrial enzyme, and phosphoenolpyruvate is transported into the cy- tosol for gluconeogenesis. In the rat and the mouse, the enzyme is cytosolic. Oxaloacetate does not cross the mi- tochondrial inner membrane; it is converted to malate, which is transported into the cytosol, and converted back to oxaloacetate by cytosolic malate dehydrogenase. In humans, the guinea pig, and the cow, the enzyme is equally distributed between mitochondria and cytosol.
The main source of GTP for phosphoenolpyruvate carboxykinase inside the mitochondrion is the reaction of succinyl-CoA synthetase (Chapter 16). This provides a link and limit between citric acid cycle activity and the extent of withdrawal of oxaloacetate for gluconeo- genesis.