Homocystinuria due to cystathionine synthase deficiency: the metabolism of L-methionine.

Abstract

Patients with homocystinuria due to cystathionine synthase deficiency have an impaired capacity to convert the sulfur of orally administered L-methionine, but not of L-cysteine, to urinary inorganic sulfate. This observation suggests that cystathionine formation is an obligatory step in the human catabolism of methionine to inorganic sulfate. The patients were able to convert a small amount of L-methionine to inorganic sulfate, possibly through residual hepatic cystathionine synthase activity. The urinary excretion of inorganic sulfate after the administration of a single dose of L- methionine distinguished the homozygote for cystathionine synthase deficiency from control subjects. The responses of two heterozygous subjects were within the control range. The administration of L-methionine to a patient with cystathionine synthase deficiency did not increase the urinary excretion of homocystine markedly. Abnormal amounts of methionine and methionine sulfoxide accumulated in the plasma, and were excreted in large quantities in the urine for an abnormally long time after L-methionine supplementation had been discontinued. Homocystine is not necessarily the most abundant abnormal S-containing compound in the urine of these patients. During L-methionine supplementation excessive amounts of bound methionine and of unidentified neutral S were detected in the urine. Their quantities exceeded that of the homocystine.