Preparation of a soluble 58kDa-3-hydroxy-3-methylglutaryl CoA reductase from liver microsomes and its inhibition by ethoxysilatrane, a hypocholesterolemic compound
Molecular and Cellular Biochemistry(1992)
摘要
On repeated thawing at room temperature of frozen preparations of heavy microsomes from rat livers, HMGCoA reductase activity
was solubilized due to limited proteolysis. This soluble enzyme was partially purified by fractionation with ammonium sulfate
and filtration on Sephacryl S-200 column. The active enzyme was coeluted with a major 92 kDa-protein and was identified as
a 58kDa-protein after separation by SDS-PAGE and immunoblotting. Ethoxysilatrane, a hypocholesterolemic compound, which decreased
the liver-microsomal activity of HMGCoA reductase on intra-peritonial treatment of animals, showed little effect on the enzyme
activity with isolated microsomes or the 50kDa-soluble enzyme when added in the assay. But it was able to inhibit the activity
of the soluble 58kDa-enzyme in a concentration-dependent, reversible manner. Cholesterol and an oxycholesterol were without
effect whereas chlorophenoxyisobutyrate and ubiquinone showed small inhibition under these conditions. The extra region that
links the active site domain (50kDa protein) to the membrane, present in the 58kDa-protein appears to be involved in mediating
the inhibition by silatrane.
更多查看译文
关键词
ethoxysilatrane,HMGCoA reductase,mevalonate biosynthesis
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要