Glycolysis is the lysis, or splitting, of one molecule of glucose into two molecules of pyruvate, producing a net gain of two ATP molecules. Pyruvate can then be used in anaerobic (fermentation) or aerobic (respiration) metabolism. The glycolysis pathway and the genes involved are illustrated here.

During glycolysis, Tpi1p (triose phosphate isomerase) catalyzes the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (3, 6). It is required for growth on glucose as the sole carbon source (6). In Saccharomyces cerevisiae, Tpi1p is an abundant glycolytic enzyme that makes up about 2% of the soluble cellular protein (2).

Tpi1p functions as a homodimer (7) and the active site residues include Glu165, His95, and Lys12. The catalytic site Glu and His residues are thought to extract and donate protons during catalysis (7, 8). The sequence around the active site residues is fully conserved in a number of organisms including chicken, yeast and Trypanosoma brucei (9).

The expression of TPI1 may be regulated by the transcriptional activators Reb1p, Rap1p, and Gcr1p that bind sites in the 5' non-coding region of TPI1. However, Gcr1p is able to activate gene expression in the absence of Reb1p or Rap1p. Therefore, it has been suggested that Gcr1p is required for activation of TPI1 and that the role of Reb1p and Rap1p, which bind adjacent to Gcr1p-binding sites, may be to facilitate or modulate Gcr1p binding in vivo (2).

In humans, deficiency of triosephosphate isomerase (TPI1) (OMIM) causes haemolytic anaemia coupled with progressive, severe neurological disorder (10).

Last updated: 2005-08-09