Deranged B 12 metabolism: Effects on sulfur amino acid metabolism

Abstract

Several enzymes have been studied in the tissues of a patient who had a combination of increased homocystine and cystathionine and decreased methionine in plasma, tissues, and urine. This patient specifically lacked activity of N 5-methyltetrahydrofolate-homocysteine methyltransferase. In addition, the patient excreted an increased amount of methylmalonic acid. His liver had an abnormally low methylmalonyl-CoA isomerase activity unless supplemented with deoxyadenosyl-B 12. These findings, as well as others presented elsewhere (3, 4), indicate that the deficient enzyme activities were due to lack of the suitable B 12-containing coenzymes rather than to primary lack of the apoenzymes. Deficient activity of cystathionine synthase or cystathionase, which often cause homocystinuria and cystathioninuria, respectively, are ruled out in this patient. Amino acid concentrations and enzyme activities have been measured also in the tissues of a second patient with many biochemical abnormalities similar to those found in the first patient. The findings indicate that remethylation of homocysteine by N 5-methyltetrahydrofolate methyltransferase, under at least some conditions, may be a physiologically important reaction.