The evolution of hexokinases.

Recent advances in the knowledge of the structural and functional aspects of the enzymes catalyzing sugar phosphorylation by ATP are reviewed. Hexokinases may exist, mainly in prokaryotes, as sugar-specific kinases (glucokinase, fructokinase, mannokinase) or as ubiquitous hexose-kinases which are relatively unspecific for the natural hexoses. Enzymes presenting intermediate specificity (e.g. mannofructokinases) have been also described. With a few exceptions, the molecular mass of a variety of hexokinases may be either 25 kDa, 50 kDa or 100 kDa. The smaller hexokinases have been found in some microorganisms whereas the 50 kDa enzymes are found (with only one exception) in most invertebrates and in a particular isozyme from vertebrates (hexokinase D). The 100 kDa enzymes are restricted to vertebrates (hexokinases A, B and C). These facts have led to the speculation that gene duplication events have played an important role in the evolutionary development of the hexokinases from present day organisms. The fact that the 100 kDa hexokinases are allosterically inhibited by the product, glucose 6-P, may indicate that a duplicated active site has evolved to a regulatory binding site. Comparisons of the amino acid sequence of a few peptides from hexokinase C are presented to support the gene duplication hypothesis. Also, partial sequence comparisons of vertebrate hexokinases with the sequences of two hexokinase isozymes from yeast show strong similarities suggesting a rather slow amino acid substitution rate of homologous genes.