Isolation and identification of methylcitrate, a major metabolic product of propionate in patients with propionic acidemia.

The metabolic products of propionate metabolism in man were studied by determining the pattern of isotope in the urine following the intravenous injection of [lJ%]propionate. A major peak of radioactivity not present in control subjects was found in an organic acid in two patients with propionic acidemia and a patient with methylmalonic acidemia. This labeled compound was characterized as methylcitrate. Methylcitrate excretion was appreciable in patients with defective propionic acid metabolism and could be detected without administration of isotope. Methylcitrate is considered to be formed from the condensation of propionyl-CoA and oxalacetate. It could be involved in the pathogenesis of the clinical manifestations of these conditions.