Studies of a 31-year-old man with proven partial deficiency of hepatic methionine adenosyltransferase (MAT) activity have been continued. Identified abnormal metabolites in his bodily fluids, urine, and/or breath include: L-methionine-d-sulfoxide, 4- methylthio-2-oxo-butyrate, 3-methylthiopropionate, dimethylsulfide, and a mixed disulfide CH3S-SX, the structure of which is still under investigation. Balance studies have permitted calculation of the fluxes of methyl- and sulfur-containing compounds and shown that: In spite of the deficient activity of hepatic MAT, the patient forms a normal amount of the product of this enzyme, S-adenosylmethionine (SAM). In spite of the normal rate of formation of SAM, the patient does not convert methionine sulfur to sulfate at a normal rate. In spite of his high body load of methionine, the patient conserves methionine by N5- methyltetrahydrofolate-dependent methylation of homocysteine. The later observations are explained in terms of the regulatory effects of SAM on cystathionine synthase and methylenetetrahydrofolate reductase. In the presence of 20- to 50-fold elevations of methionine, the transamination pathway metabolizes about 20% of the normal methionine intake of this patient, although the transamination pathway is clearly not sufficiently active to prevent the accumulation of methionine.
