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  • Title: [Biosynthesis of mevalonic acid, sterols and bile acids from acetyl-CoA and malonyl-CoA in the human liver].
    Author: Klimov AN, Poliakova ED, Klimova TA, Dizhe EB, Vasil'eva LE.
    Journal: Biokhimiia; 1983 Nov; 48(11):1862-9. PubMed ID: 6661459.
    Abstract:
    The biosynthesis of mevalonic acid, squalene, sterols, bile and fatty acids from [2-14C]malonyl-CoA and [1-14C]acetyl-CoA were studied. The activities of 3-hydroxy-3-methylglutaryl-CoA-reductase (GMG-CoA reductase) and acetyl-CoA carboxylase in subcellular fractions of human liver were determined. The livers of humans were used within 1.5-3 hours after clinical death. It was found that in all fractions studied (i.e. cell-free, 700 g, postmitochondrial, microsomal, cytosol) malonyl-CoA is incorporated into mevalonic acid more intensively than acetyl-CoA. The specific activity of GMG-CoA reductase in the microsomal and soluble fractions was essentially the same. Calculation of enzymatic activity per 1 g of wet mass of tissue showed that the bulk of activity is bound to the cytosol (soluble fraction) Malonyl-CoA can also act as a precursor of squalene, lanosterol, cholesterol and bile acids. The rate of malonyl-CoA incorporation into these compounds is practically the same as that of [2-14C] mevalonate but significantly exceeds that of acetyl-CoA at equal molar ratios of both substrates. Incorporation of malonyl-CoA into cholesterol occurs much more intensively in human liver than in rat liver, the cholesterol radioactivity reaching 18% of the total unsaponified fraction. Malonyl-CoA is a better substrate than acetyl-CoA both for fatty acid and for mevalonate, sterol and bile acid synthesis.
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