Pyruvate carboxylase uses a covalently attached biotin cofactor which is used to catalyze the ATP– dependent carboxylation of pyruvate to oxaloacetate in two steps. Author information: (1)School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, WA 6009, Australia. Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. Three to four families of nuclear genes encode different isoforms of phosphoenolpyruvate (PEP) carboxylase (PEPC): C4-specific, C3 or etiolated, CAM and root forms. Pyruvate carboxylase (PC; E.C. is a multifunctional, biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate. The International Journal of Biochemistry & Cell Biology 2008 , 40 (9) , 1743-1752. This is a very important anaplerotic reaction, replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways. The overall reaction is accomplished by the coupling of two half reactions occurring at two spatially distinct catalytic domains by the translocation of a carrier domain, resulting in a net transfer of CO2 from bicarbonate to pyruvate. Human PC is a tetramer composed of identical subunits (Barden et al., 1975). In contrast to many higher organisms where the anaplerotic pyruvate carboxylase is a mitochondrial enzyme, its location is exclusively cytosolic in S. cerevisiae [20] . More specifically pyruvate carboxylase is activated by acetyl-CoA. The regulation of yeast pyruvate carboxylase by acetyl-coenzyme A and L-aspartate. Because acetyl-CoA is an important metabolite in the TCA cycle which produces a lot of energy, when concentrations of acetyl-CoA are high organisms use pyruvate carboxylase to channel pyruvate away from the TCA cycle. Regulation of Pyruvate Carboxylase Activity by Calcium in Intact Rat Liver Mitochondriae (Received for publication, July 10, 19GS) GEORGE A. I