Methylmalonyl-CoA mutase is a key enzyme in intermediary metabolism, and children
deficient in enzyme activity have severe metabolic acidosis. We found that nitric oxide (NO)
inhibits methylmalonyl-CoA mutase activity in rodent cell extracts. The inhibition of enzyme
activity occurred within minutes and was not prevented by thiols, suggesting that enzyme
inhibition was not occurring via NO reaction with cysteine residues to form nitrosothiol
groups. Enzyme inhibition was dependent on the presence of substrate, implying that NO …