[Decarboxylation of malonyl-CoA and biosynthesis of mevalonic acid in rat liver].
Biosynthesis of mevalonic acid (MVA), total formation of 14CO2 from [1,3-14C]malonyl-CoA and the activity of malonyl-CoA decarboxylase in subcellular fractions of rat liver were studied. The dependence of the rate of MVA biosynthesis on malonyl-CoA concentration was found to be linear both in 140,000 g supernatant and solubilized microsomal fractions. It was shown that in a composite system (140,000 g supernatant fraction added to washed microsomes, 10 : 1) the optimal concentration ratio for the substrates of MVA biosynthesis (malonyl-CoA and acetyl-CoA) is 1 to 2. In the absence of acetyl-CoA decarboxylation of [1,3-14C]malonyl-CoA was prevalent. In all subcellular fractions studied decarboxylation of [1,3-14C]malonyl-CoA prevailed over its incorporation into MVA, total non-saponified lipid fraction and fatty acids. The degree of malonyl-CoA, decarboxylation was not correlated with the rate of its incorporation into MVA, i. e. the increase in the 14CO2 formation was not accompanied by stimulation of [1,3-14C]malonyl-CoA incorporation either into MVA or into total non-saponified lipid fractions. The incorporation of [1-14C]acetyl-CoA into MVA under the same conditions was considerably lower than that of [1,3-14C]malonyl-CoA. In all subcellular fractions under study the activity of malonyl-CoA decarboxylase was found. The experimental data suggest that a remarkable part of malonyl-CoA is incorporated into MVA without preliminary decarboxylation. A possible role of malonyl-CoA decarboxylase as an enzyme which protects the cell against accumulation of malonyl-CoA and its immediate metabolites -- malonate and methylmalonyl-CoA is disucssed.
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide; D002262:Carboxy-Lyases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008798:Mevalonic Acid / Q000096:biosynthesis*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats
D000214:Acyl Coenzyme A; D002245:Carbon Dioxide; D008316:Malonyl Coenzyme A; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D008798:Mevalonic Acid
Dekarboksilirovanie malonil-koA i biosintez mevalonovoĭ kisloty v pecheni krys.