Genetic and biochemical aspects of yeast sterol regulation involving 3-hydroxy-3-methylglutaryl coenzyme A reductase
| Autor: | James F. Downing, Martin Bard |
|---|---|
| Rok vydání: | 1981 |
| Předmět: |
Squalene
7-Dehydrocholesterol reductase Coenzyme A Saccharomyces cerevisiae Mevalonic Acid Regulatory site Reductase Haploidy Microbiology Feedback chemistry.chemical_compound Ergosterol biology biology.organism_classification Diploidy Enzyme assay Sterol Sterols chemistry Biochemistry biology.protein lipids (amino acids peptides and proteins) Hydroxymethylglutaryl CoA Reductases Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | Journal of general microbiology. 125(2) |
| ISSN: | 0022-1287 |
| Popis: | Determinations of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in haploid strains and diploid hybrids of wild-type Saccharomyces cerevisiae revealed that a genetic basis exists for control of this key regulatory enzyme in which low enzyme activity is phenotypically dominant to high enzyme activity. These observations suggested the existence of an inhibitor of reductase activity or a suppressor of enzyme synthesis. Feeding studies using an early sterol intermediate (mevalonolactone) and end-product sterol (ergosterol) indicated that a secondary regulatory site in this pathway operates to decrease the activity of HMG-CoA reductase. This diminution of activity was paralleled by increases in the accumulation of squalene, suggesting that this intermediate (or another isoprenoid derivative) may also play a significant role in the in vivo regulation of sterol biosynthesis. Lastly, feedback inhibition of HMG-CoA reductase by ergosterol was demonstrated in a yeast mutant which is permeable to this sterol. These studies showed that yeast can serve as a eukaryotic model system for a combined biochemical and genetic investigation into the factors which control the activity of HMG-CoA reductase. |
| Databáze: | OpenAIRE |
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