Glutaric aciduria type II: evidence for a defect related to the electron transfer flavoprotein or its dehydrogenase.
Incubation of intact fibroblasts from a patients with glutaric aciduria type II with [2-14C]riboflavin showed normal synthesis of flavin mononucleotide and flavin adenine dinucleotide. This is taken as evidence for normal transport of riboflavin into the cells and normal activity of riboflavin kinase (EC 2.7.1.26) and flavin mononucleotide adenylyltransferase (EC 2.7.7.2). The ability of intact fibroblasts to oxidize 1-14C-fatty acids and [6-14C]lysine is impaired in the patient which together with the urinary excretion pattern of organic acids indicates a defective dehydrogenation of fatty acid acyl-CoAs and glutaryl-CoA. However, dehydrogenation of (C6-C10) fatty acid acyl-CoA derivatives and glutaryl-CoA was normal when the dehydrogenases were measured in fibroblast homogenate with artificial electron acceptors. In vivo, these dehydrogenases transfer their electrons to CoQ10 in the main electron transport chain via electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase. Glutaric aciduria type II fibroblasts showed very diminished activity when the glutaryl-CoA dehydrogenase activity was measured without artificial electron acceptor but with intact endogenous electron transport system. As the NADH and succinate oxidation seems normal in glutaric aciduria type II patients, this is strong evidence for a defect in either the electron transfer flavoprotein or the electron transfer flavoprotein dehydrogenase.
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology*; D004579:Electron Transport; D044927:Electron-Transferring Flavoproteins; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000096:biosynthesis; D005182:Flavin-Adenine Dinucleotide / Q000096:biosynthesis; D005420:Flavoproteins / Q000172:deficiency*; D005977:Glutarates / Q000652:urine*; D050770:Glutaryl-CoA Dehydrogenase; D006801:Humans; D007506:Iron-Sulfur Proteins; D008239:Lysine / Q000378:metabolism; D009097:Multienzyme Complexes; D010088:Oxidoreductases / Q000172:deficiency* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012256:Riboflavin / Q000378:metabolism
D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids; D005420:Flavoproteins; D005977:Glutarates; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D010088:Oxidoreductases; D044943:Fatty Acid Desaturases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; D008239:Lysine; D012256:Riboflavin