Pyruvate carboxylase (PC) is a regulated mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, a critical transition that replenishes citric acid cycle intermediates and facilitates other biosynthetic reactions that drive anabolism. Its deficiency causes multiorgan metabolic imbalance that predominantly manifests with lactic acidemia and neurological dysfunction at an ...

Evidence is presented for the specific in vivo and in vitro inhibition of isovaleryl CoA dehydrogenation by hypoglycin A and its derivative, alpha-ketomethylenecyclopropylpropionic acid. alpha-Methylbutyryl CoA dehydrogenation was also impaired, but the degree of inhibition was much lower. Isobutyryl CoA dehydrogenation was not inhibited. 4-Pentenoic acid inhibited none of these reactions. It i...

Many inborn errors of metabolism are characterized by an increase in the concentrations of various carboxylic acids in blood and urine. For example, the metabolic disorders propionic acidemia [ 11, methylmalonic aciduria [ 2,3], maple syrup urine disease [4], isovaleric acidemia [ 41 and glutaric aciduria type II [ 5,6] show increased amounts of volatile carboxylic acids in blood or urine. Proc...

We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully (13)C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the l...

An 18-month-old girl presented with recurrent episodes of encephalopathy, starting from the third postnatal day, and delayed development. Her parents were nonconsanguineous. She had microcephaly, generalized hypotonia, brisk stretch reflexes, extensor plantar response, choreiform movements, and dystonia of hands and feet. Evaluation showed metabolic acidosis and hyperammonemia. Tandem mass spec...

We report a method for rapid prenatal detection of methylmalonic acidemia, consisting of measuring methylmalonly-CoA mutase (EC 5.4.99.2) activity in non-cultured amniotic cells and measuring the concentration of methylmalonate in the amniotic fluid. Immediate stabilization of the mutase activity in the non-cultured amniotic cell by its coenzyme adenosycobalamin, and use of methylmalonyl-CoA wi...