Effect of lipoic acid in a patient with defective activity of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase.
Lactic acidosis and accumulation of 3-hydroxybutyrate and other citric acid cycle intermediates were found in an infant with a lethal syndrome of metabolic acidosis and renal tubular acidosis. Nevertheless, the patient was relatively well for 4 mo of life. The activity of the pyruvate dehydrogenase complex, 2-oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase were all reduced to levels 9 to 29% of control. In contrast, the activity of lipoamide dehydrogenase was normal. The conversion of 1-14C-leucine and 1-14C-valine to 14CO2 and of U-L-14C-valine to its major metabolic product 3-hydroxyisobutyric acid by fibroblasts derived from the patient was less than 5% of control. Cultivation of the patient's fibroblasts in medium enriched with lipoic acid markedly improved these in vitro conversions of leucine and valine.
Yoshida
I
I
Department of Pediatrics and Child Health, Kurume University, Japan.
Sweetman
L
L
Kulovich
S
S
Nyhan
W L
WL
Robinson
B H
BH
D020155:3-Hydroxybutyric Acid; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000140:Acidosis, Lactic / Q000201:enzymology* / Q000209:etiology; D000141:Acidosis, Renal Tubular / Q000201:enzymology* / Q000209:etiology; D002952:Citric Acid Cycle / Q000502:physiology*; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism*; D007223:Infant; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000150:complications*; D015323:Pyruvate Metabolism, Inborn Errors / Q000150:complications*; D008063:Thioctic Acid / Q000494:pharmacology*
D006885:Hydroxybutyrates; D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D008063:Thioctic Acid; D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D020155:3-Hydroxybutyric Acid