E. Kang, P. J. Snodgrass, P. Gerald
Dec 1, 1972
Citations
0
Influential Citations
55
Citations
Journal
Pediatric Research
Abstract
Extract: Metabolism of 14C-propionate and methylmalonate was severely curtailed in fibro-blasts cultured from an infant with massive transient hyperammonemia (1370 $mUg/100 ml), severe metabolic acidosis, and excretion of large amounts of methylmalonic acid (580 mg at 24°). Metabolism of succinate was normal.Metabolism of methylmalonate was not enhanced by the addition of excessive amounts of the cofactor, 5′-deoxyadenosylcobalamin (DBCC). The DBCG content of the liver was within normal limits.Homogenates of liver and fibroblasts metabolized methylmalonate approximately one-half as well as control samples when tritiated racemic methylmalonyl coenzyme A (CoA) was added. Inasmuch as L-methylmalonyl-CoA and not D-methylmalonyl-CoA is the substrate for the enzyme, methylmalonyl-CoA mutase, which converts L-methylmalonyl-CoA to succinyl-CoA, this indicates that the mutase was intact.Mitochondrial homogenate from liver, in contrast to normal samples, did not incorporate tritium during the metabolism of synthetic methylmalonyl-CoA, which indicates that activity of racemase was deficient.Activities of the urea cycle enzymes were low but not rate limiting.Speculation: A diet low in isoleucine, threonine, methionine, and valine may offer a rational therapeutic approach to other affected patients. The hyperammonemia observed resembles that reported in propionyl-CoA carboxylase deficiency and Reye's syndrome, which raises the possibility of a common denominator in these several disorders.