Anabolic function of the type II isozyme of hexokinase in hepatic lipid synthesis

The mRNA encoding the Type II isozyme of hexokinase was markedly elevated i n livers of transgenic mice overexpressing the transcriptionally active nuc lear form of sterol regulatory element binding protein-1a (nSREBP-1a), but not in transgenic mice overexpressing the nSREBP-1c or nSREBP-2 isoforms. C ellulose acetate electrophoresis and immunoblotting results confirmed selec tive increase of the Type II isozyme in livers of transgenic mice expressin g nSREBP-1a, SREBP-1a has previously been shown to activate transcription o f genes encoding enzymes involved in biosynthesis of fatty acids and glycer olipids and to a lesser extent the enzymes of cholesterol biosynthesis. Thu s, these results are consistent with the view that the Type II isozyme serv es an anabolic function, providing precursors and reducing equivalents requ ired for increased rates of hepatic lipid synthesis, (C) 2000 Academic Pres s.