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 in livers of transgenic mice overexpressing the transcriptionally active nuclear form of sterol regulatory element binding protein-1a (nSREBP-1a), but not in transgenic mice overexpressing the nSREBP-1c or nSREBP-2 isoforms. Cellulose acetate electrophoresis and immunoblotting results confirmed selective increase of the Type II isozyme in livers of transgenic mice expressing nSREBP-1a. SREBP-1a has previously been shown to activate transcription of genes encoding enzymes involved in biosynthesis of fatty acids and glycerolipids and to a lesser extent the enzymes of cholesterol biosynthesis. Thus, these results are consistent with the view that the Type II isozyme serves an anabolic function, providing precursors and reducing equivalents required for increased rates of hepatic lipid synthesis.
Sebastian
S
S
Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Horton
J D
JD
Wilson
J E
JE
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008055:Lipids; D009687:Nuclear Proteins; D020033:Protein Isoforms; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D006593:Hexokinase