Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase
| Autor: | A A Kandutsch, E J Parish, S E Saucier, F R Taylor, E P Shown |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Binding protein
Coenzyme A Ligand binding assay Cell Biology Biology Reductase Biochemistry Molecular biology Hydroxymethylglutaryl-CoA reductase Sterol chemistry.chemical_compound chemistry Oxysterol binding polycyclic compounds lipids (amino acids peptides and proteins) Oxysterol-binding protein Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 259:12382-12387 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(18)90757-x |
| Popis: | Support for the role of a cytosolic oxysterol-binding protein in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was obtained by correlating the relative binding affinities of a wide range of oxysterols to their potency in suppressing HMG-CoA reductase activity in mouse fibroblast cell cultures. Forty-seven oxysterols encompassing a 100-fold range of activity in both assays were tested and the two parameters were closely correlated for 35 of the sterols. Twelve sterols showed poor binding when compared to their ability to suppress HMG-CoA reductase activity in cell cultures. Among these were seven sterols with a ketone function at C-3. For this group, the discrepancy could be explained by their rapid conversion within cells to the 3 beta-hydroxy derivatives which have a much higher affinity for the binding protein. One sterol with 3-keto-4-ene grouping was not reduced to its 3 beta-hydroxy derivative in cells and thereby showed no discrepancy in the two assays. The remaining five sterols exhibiting discordant activities in the two tests contained 4,4-dimethyl moieties and were relatively weak suppressors of HMG-CoA reductase activity. Cellular metabolism of these sterols was not detected. Possible reasons for their apparent inactivity in the binding assay are discussed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|