GAL10 encodes a bifunctional enzyme with mutarotase and UDP galactose 4-epimerase activities (2, 3). Both of these functions are key in the process of galactose catabolism; mutarotase converts beta-D-galactose into its alpha form and galactose 4-epimerase catalyzes the reversible conversion between UDP-galactose and UDP-glucose (4, 2). Crystal structure analysis reveals that the galactose 4-epimerase domain, encoded by the N-terminus of the protein, is separated from the C-terminal mutarotase domain by a simple Type II turn (5). Loss of Gal10p activity renders cells unable to grow when galactose is the sole carbon source (6).

Although S. cerevisiae Gal10p is a bifunctional enzyme, in most organisms the epimerase and mutarotase activities are found on separate peptides. Mutations in human GALE (OMIM), the functional homolog of the galactose 4-epimerase domain of yeast Gal10p, have been associated with the disease galactose epimerase deficiency/galactosemia III (OMIM), the mild peripheral form of which is benign while the severe general form can cause impaired liver function and mental retardation (7 and references therein).

All the galactose structural genes (GAL1, GAL10, GAL7, GAL2) are coordinately regulated at the level of transcription in response to galactose by Gal4p, Gal80p, and Gal3p (4, 8, and reviewed in 9). Regardless of carbon source, the Gal4p transcriptional activator is bound as a dimer to upstream activation sites found in the promoters of the GAL genes. In the presence of galactose, Gal3p sequesters the transcriptional repressor Gal80p in the cytoplasm, thereby relieving inhibition of Gal4p and resulting in GAL gene expression (10). In the absence of galactose, Gal80p remains bound as a dimer, to Gal4p, preventing Gal4p from recruiting other factors of the Pol II transcription machinery (reviewed in 9).

Last updated: 2006-10-12