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- W2083662313 abstract "A new analog of mevalonic acid, 3,5-dihydroxy-3,4,4-trimethylvaleric acid, was synthesized from 4-bromoacetoxy-3,3-dimethyl-2-butanone by an internal Reformatsky reaction. The compound strongly inhibits cholesterol biosynthesis by rat liver homogenates. The inhibitor in 4 × 10−4m (dl-form) concentration decreased incorporation of mevalonate-2-14C into cholesterol by half. In the presence of this inhibitor, 5-phosphomevalonate accumulates from mevalonic acid and allylpyrophosphates could not be detected. Accumulation of the monophosphate suggests that a major site of inhibition is at the second phosphorylation step, in which 5-phosphomevalonate is converted to 5-pyrophosphomevalonate by 5-phosphomevalonic kinase. A reaction mixture was developed for optimal accumulation of 5-phosphomevalonate. The new inhibitor provides a competitive substrate that will be useful for examining the mechanism of mevalonic kinase and phosphomevalonic kinase." @default.
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- W2083662313 date "1971-10-01" @default.
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- W2083662313 title "Inhibition of hepatic cholesterol biosynthesis by 3,5-dihydroxy-3,4,4-trimethylvaleric acid and its site of action" @default.
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- W2083662313 doi "https://doi.org/10.1016/0003-9861(71)90144-5" @default.
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