[Biosynthesis of mevalonic acid, sterols and bile acids from acetyl-CoA and malonyl-CoA in the human liver].
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.
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008798:Mevalonic Acid / Q000096:biosynthesis*; D013261:Sterols / Q000096:biosynthesis*
D000214:Acyl Coenzyme A; D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D013261:Sterols; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D008798:Mevalonic Acid
Biosintez mevalonovoĭ kisloty, sterinov i zhelchnykh kislot iz atsetil-CoA i malonil-CoA v pecheni cheloveka.