Increased excretion of lactate, glutarate, 3-hydroxyisovalerate and 3-methylglutaconate during clinical episodes of propionic acidemia.
Metabolic changes dependent upon clinical conditions were studied in an eight-month-old girl with propionyl CoA carboxylase deficiency. Only methylcitric acid and 2-methyl-3-oxovaleric acid were detected in the urine of the patient under clinically favorable conditions. During episodes of clinical decompensation, she excreted increased amounts of all the metabolites associated with this disorder. Four acetyl CoA precursors increased during clinical episodes: glutaric acid, a catabolic intermediate of lysine; 3-hydroxyisovaleric acid and 3-methylglutaconic acid, catabolic intermediates of leucine; and lactic acid. This suggests that under clinically favorable conditions the patient has an altered propionate metabolism which proceeds via normal acetyl CoA metabolism with sufficient capacity for acetyl CoA plus propionyl CoA metabolism. When the production of propionyl CoA exceeds the metabolic capacity, however, the catabolism of potent ketogenic amino acids is effectively suppressed in order to reduce acetyl CoA production.
D000592:Amino Acid Metabolism, Inborn Errors / Q000652:urine*; D002262:Carboxy-Lyases / Q000172:deficiency; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D007773:Lactates / Q000652:urine*; D019344:Lactic Acid; D043586:Methylmalonyl-CoA Decarboxylase; D011422:Propionates / Q000097:blood*; D014631:Valerates / Q000652:urine*
D005977:Glutarates; D007773:Lactates; D011422:Propionates; D014631:Valerates; D019344:Lactic Acid; C004961:beta-hydroxyisovaleric acid; C022034:3-methylglutaconic acid; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase