Localization of the gene encoding 3-hydroxy-3-methylglutaryl-coenzyme A synthase to human chromosome 5.
A series of hybrids between primary human cells and a Chinese hamster somatic cell mutant (Mev-1), defective in expression of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating, EC 4.1.3.5], has been prepared that complements the mutant defect. A technique based on differential sensitivity of this enzyme activity to inhibition by magnesium ion is described that allows the discrimination of expression of human and hamster HMG-CoA synthase in these hybrids. The results indicate a structural gene defect in expression of HMG-CoA synthase activity in Mev-1 cells. Segregation of human chromosomes that do not possess the complementing marker have allowed the assignment of human HMG-CoA synthase activity to chromosome 5. This is the second demonstrably transcriptionally regulated enzyme of cholesterologenesis to be assigned to chromosome 5, the other being HMG-CoA reductase.
Leonard
S
S
Arbogast
D
D
Geyer
D
D
Jones
C
C
Sinensky
M
M
D002874:Chromosome Mapping; D002905:Chromosomes, Human, 4-5; D005786:Gene Expression Regulation; D006801:Humans; D006822:Hybrid Cells / Q000502:physiology; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D007652:Oxo-Acid-Lyases / Q000235:genetics*; D013261:Sterols / Q000502:physiology
D013261:Sterols; D006904:Hydroxymethylglutaryl-CoA Synthase; D007652:Oxo-Acid-Lyases; D008274:Magnesium