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).

In addition to regulation of transcription (through catabolite repression), the amount of Fbp1p in the cell is regulated by mRNA and protein degradation when glucose-starved cells are replenished with glucose (7, 8). There appear to be two pathways for degradation of Fbp1p: a proteasomal pathway that acts following short-term glucose starvation and a vacuolar pathway that functions following long-term glucose starvation (3). Transcriptional regulation is effected through consensus sequences in the FBP1 promoter region for the repressor Mig1p, the activating HAP complex, and the derepressing zinc finger protein Cat8p (9, reviewed in 5).

Last updated: 2005-06-21