The first irreversible step in the intracellular metabolism of glucose involves the phosphorylation of glucose at C6. In Saccharomyces cerevisiae, this can be catalysed by three enzymes, namely the hexokinases Hxk1p and Hxk2p and the glucokinase Glk1p (6, 7, 3). All three proteins are involved in the uptake of glucose (8), however Hxk2p appears to play the main role during glucose phosphorylation in vivo, because it is the predominant isoenzyme during growth on glucose (6, 3). The HXK2 gene is expressed when yeast cells are grown on a fermentable medium using glucose, fructose or mannose as a carbon source (8, 9). When cells are shifted to a non-fermentable carbon source, the HXK2 gene is repressed and the HXK1 and GLK1 genes are rapidly de-repressed (10, 2).

Hxk2p is predominantly found in the cytosol where it is a key enzyme in glycolysis. However, Hxk2p is also found in the nucleus where it is required for the glucose-induced repression of several genes, including HXK1 and GLK1, and for glucose-induced expression of its own gene, HXK2 (2, 11, 12, 13). Interestingly, Hxk2p also plays a role in replicative cell aging because deletion of HXK2 significantly enhances yeast longevity (14).

HXK1, HXK2, and GLK1 homologs have been identified in fission yeast, rice, arabidopsis, and mammals (15, 16, 17). In pancreatic cells, human glucokinase/hexokinase IV (GCK/HK4; OMIM), a functional homolog of S. cerevisiae genes HXK1, HXK2, and GLK1, acts as a glucose sensor and is involved in regulating insulin secretion. Mutations in GCK/HK4 have been associated with the diseases, familial hyperinsulinemic hypoglycemia-3 (OMIM) and the form of late-onset noninsulin-dependent diabetes mellitus known as type II maturity-onset diabetes of the young (OMIM) (18).

Last updated: 2006-11-29