Gluconeogenesis is the process whereby glucose is synthesized from non-carbohydrate precursors, which enables yeast cells to grow on non-sugar carbon sources like ethanol, glycerol, or peptone. The reactions of gluconeogenesis, shown here, mediate conversion of pyruvate to glucose, which is the opposite of glycolysis, the formation of pyruvate from glucose. While these two pathways have several reactions in common, they are not the exact reverse of each other. As the glycolytic enzymes phosphofructokinase (Pfk1p, Pfk2p) and pyruvate kinase (Cdc19p) only function in the forward direction, the gluconeogenesis pathway replaces those steps with the enzymes pyruvate carboxylase (Pyc1p, Pyc2p) and phosphoenolpyruvate carboxykinase (Pck1p)-generating oxaloacetate as an intermediate from pyruvate to phosphoenolpyruvate-and also the enzyme fructose-1,6-bisphosphatase (Fbp1p) (reviewed in 5). Overall, the gluconeogenic reactions convert two molecules of pyruvate to a molecule of glucose, with the expenditure of six high-energy phosphate bonds, four from ATP and two from GTP. Expression of genes encoding several of the gluconeogenic enzymes is subject to glucose repression (6).

PYC1 encodes one of the two yeast pyruvate carboxylase isozymes; the other is encoded by PYC2 (7, 8, 1). Pyruvate carboxylase produces oxaloacetate from pyruvate, a process which in many organisms is mitochondrial, but in yeast is cytosolic (9, 10). No obvious phenotype is observed when either PYC1 or PYC2 is disrupted singly, but when both genes are disrupted cells are unable to grow with glucose as the sole carbon source unless aspartate is added to the medium instead of ammonia (8). PYC1 and PYC2 are differentially regulated, with expression influenced by growth phase and carbon source (2). Expression of PYC1 but not PYC2 is also regulated by the type of nitrogen source independently of the carbon source in the medium (11). The RTG genes may contribute to control of PYC1 expression (12). Mutations in PC, the human pyruvate carboxylase gene (OMIM), are associated with pyruvate carboxylase deficiency and ataxia with lactic acidosis (OMIM) (3).

Last updated: 2005-07-22