ABSTRACT
Malonic acid is a potent inhibitor of many metabolic pathways as well as playing its classic role as an inhibitor of succinic acid dehydrogenase in the citric acid cycle (Figures 12.1 and 12.2). Its accumulation might be expected to disrupt the metabolism of many compounds. Succinic aciduria has been reported in malonyl CoA decarboxylase deficiency [1,2], a disorder described in patients with metabolic acidosis and a propensity for hypoglycemia. Hypoglycemia might be expected to result from that fact that malonyl CoA is an inhibitor of pyruvate carboxylase [3]. It could also result, along with dicarboxylic aciduria, from abnormality in fatty acid oxidation, a consequence of the fact that malonyl CoA is an inhibitor of carnitine palmitoyl transferase I [4], an enzyme necessary for the effective transport of long-chain fatty acids across the mitochondrial membrane to where the enzymes of -oxidation are situated. Inhibition of glutaryl CoA dehydrogenase by malonyl CoA has also been reported [2], and this would be expected to lead to accumulation of glutaric acid and the hydroxyglutaric acids. Methylmalonic acid accumulation would be expected because malonyl CoA is an inhibitor of methylmalonyl CoA mutase [5].
