The multiple acyl-coenzyme A dehydrogenation disorders, glutaric aciduria type II and ethylmalonic-adipic aciduria. Mitochondrial fatty acid oxidation, acyl-coenzyme A dehydrogenase, and electron transfer flavoprotein activities in fibroblasts.
The multiple acyl-coenzyme A (CoA) dehydrogenation disorders (MAD) include severe (S) and mild (M) variants, glutaric aciduria type II (MAD:S) and ethylmalonic-adipic aciduria (MAD:M). Intact MAD:M mitochondria oxidized [1-14C]octanoate, [1-14C]palmityl-CoA, and [1,5-14C]glutarate at 20-46% of control levels; MAD:S mitochondria oxidized these three substrates at 0.4-18% of control levels. In MAD:M mitochondria, acyl-CoA dehydrogenase (ADH) activities were similar to control, whereas MAD:S ADH activities ranged from 38% to 73% of control. Electron transfer flavoprotein (ETF) activities in five MAD:M cell lines ranged from 29 to 51% of control (P less than 0.01); ETF deficiency was the primary enzymatic defect in two MAD:M lines. In four MAD:S patients, ETF activities ranged from 3% to 6% of control (P less than 0.001); flavin adenine dinucleotide addition increased residual ETF activity from 4% to 21% of control in a single MAD:S line (P less than 0.01). Three MAD:S patients had ETF activities ranging from 33 to 53% of control; other investigators found deficient ETF-dehydrogenase activity in these MAD:S and three of our MAD:M cell lines.
D000214:Acyl Coenzyme A / Q000378:metabolism; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism*; D000272:Adipates / Q000652:urine*; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D004579:Electron Transport; D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D005977:Glutarates / Q000652:urine*; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008314:Malonates / Q000652:urine*; D008928:Mitochondria / Q000201:enzymology; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013552:Swine
D000214:Acyl Coenzyme A; D000272:Adipates; D002210:Caprylates; D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids; D005420:Flavoproteins; D005977:Glutarates; D008314:Malonates; D013386:Succinates; C034681:octanoyl-coenzyme A; D005182:Flavin-Adenine Dinucleotide; D010171:Palmitoyl Coenzyme A; C038080:ethylmalonic acid; C029900:adipic acid; D019802:Succinic Acid; D044944:Acyl-CoA Dehydrogenases; C031492:octanoic acid