The microsomal dicarboxylyl-CoA synthetase.
Dicarboxylic acids are products of the omega-oxidation of monocarboxylic acids. We demonstrate that in rat liver dicarboxylic acids (C5-C16) can be converted into their CoA esters by a dicarboxylyl-CoA synthetase. During this activation ATP, which cannot be replaced by GTP, is converted into AMP and PPi, both acting as feedback inhibitors of the reaction. Thermolabile at 37 degrees C, and optimally active at pH 6.5, dicarboxylyl-CoA synthetase displays the highest activity on dodecanedioic acid (2 micromol/min per g of liver). Cell-fractionation studies indicate that this enzyme belongs to the hepatic microsomal fraction. Investigations about the fate of dicarboxylyl-CoA esters disclosed the existence of an oxidase, which could be measured by monitoring the production of H2O2. In our assay conditions this H2O2 production is dependent on and closely follows the CoA consumption. It appears that the chain-length specificity of the handling of dicarboxylic acids by this catabolic pathway (activation to acyl-CoA and oxidation with H2O2 production) parallels the pattern of the degradation of exogenous dicarboxylic acids in vivo.
D000818:Animals; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D002994:Clofibrate / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D003998:Dicarboxylic Acids; D010710:Phosphates; C036836:dodecanedioic acid; D010088:Oxidoreductases; C047028:dicarboxylic acid-CoA oxidase; D003066:Coenzyme A Ligases; C047027:dicarboxylic acid-CoA synthetase; D002994:Clofibrate