GPM1 encodes phosphoglycerate mutase (4), which is a tetrameric enzyme responsible for the conversion of 3-phospholycerate to 2-phosphoglycerate during glycolysis (5,6), and the reverse reaction during gluconeogenesis (7,3). As such, Gpm1p is required for growth on glucose, glycerol, or ethanol as a sole carbon source (4). Homozygous diploid gpm1 mutant cells fail to sporulate, an observation indicating that gluconeogenesis is required for sporulation (8).

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 9). 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.

The GPM1 promoter has been extensively characterized (2). It contains separate regulatory elements for transcriptional activation and repression: two upstream repressing (URS) sites and one UAS (upstream activating) site are found upstream of the translational start codon. This region also contains binding sites for the transcriptional activator of glycolysis Gcr1p and the activator Rap1p.

The active-site residues of Gpm1p (His8, Arg59, and His181) have also been identified (10, 11). Two yeast sequences homologous to GPM1, designated GPM2 and GPM3, contain these active site residues. However, neither gene complements a gpm1 deletion mutant and it has been demonstrated that glycolysis is not affected in either the gpm2 or gpm3 single or double deletion mutants. In fact, neither mutation confers an obvious phenotype, suggesting that both GPM2 and GPM3 likely evolved from duplication events and appear to constitute non-functional homologs of GPM1 in yeast (12).

Last updated: 2005-07-22