Metabolism of branched-chain amino acids in fibroblasts from patients with maple syrup urine disease and other abnormalities of branched-chain ketoacid dehydrogenase activity.
The metabolism of branched-chain amino acids was studied in cultured fibroblasts from patients with branched-chain ketoacid dehydrogenase deficiency using 1-14C- and UL-14C-leucine and valine. The formation of 14CO2 from 1-14C-valine or 1-14C-leucine was 1-3% of normal. In fibroblasts of patients with associated lactic acidemia the values were 4-29% of control. Analysis of organic acid products revealed that in both patients and controls the amount of labeled alpha-ketoisovalerate recovered after incubation with 1-14C-valine was one-third of the amount of alpha-ketoisocaproate recovered after incubation with 1-14C-leucine. Very little alpha-hydroxyisocaproate was produced, while the amount of alpha-hydroxyisovalerate was about 10% of the alpha-ketoisovalerate. Unexpectedly beta-hydroxyisobutyrate was found to be the major metabolic product of UL-14C-valine in normal fibroblasts. Large accumulations of beta-hydroxyisovalerate were found in normal fibroblasts using UL-14C-leucine. There were little or no conversions to these compounds in fibroblasts of patients with branched-chain ketoacid dehydrogenase deficiency. There were substantial conversions in the patients in whom dehydrogenase deficiency was associated with lactic acidemia.
Yoshida
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I
Sweetman
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Nyhan
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WL
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D002460:Cell Line; D002853:Chromatography, Liquid; D005347:Fibroblasts / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D014633:Valine / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D002250:Carbon Radioisotopes; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine; D014633:Valine