Congenital methylmalonic acidemia: a variant of the B12 'non-responsive' form with evidence for reduced affinity of methylmalonyl-CoA mutase for its B12-coenzyme.
Methylmalonate metabolism was investigated in fibroblasts and leukocytes of two unrelated patient with a B12-nonresponsive type of congenital methylmalonic acidemia. Intact fibroblasts from both patients showed a defective metabolism of methyl-14 c-malonate to 14CO2, whereas no such defect was found in their intact peripheral leukocytes. In disrupted fibroblasts, the conversion of methylmalonyl coenzyme A to succinyl coenzyme A was markedly reduced but was completely normalized by the addition of 5'-deoxyadenosylcobalamin (AdoCb1; 10(-5) mol/l), the specific coenzyme of methylmalonyl coenzyme A mutase. Assays with decreasing concentrations of AdoCbl (10(-5)-10(-11) mol/l) suggested a reduced affinity of the mutase apoenzyme for its coenzyme, implicating yet another variant of this heterogeneous disease.
D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D007535:Isomerases / Q000378:metabolism*; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology; D008314:Malonates / Q000378:metabolism*; D008764:Methylmalonic Acid / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism*; D014805:Vitamin B 12 / Q000494:pharmacology / Q000627:therapeutic use*
D008314:Malonates; D008764:Methylmalonic Acid; D007535:Isomerases; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12