Methanethiol and dimethylsulfide formation from 3-methylthiopropionate in human and rat hepatocytes.

This study was designed to investigate the metabolism of methanethiol, and the involvement of methanethiol and its metabolites in the transamination pathway of methionine. Gaseous methanethiol, methanethiol-mixed disulfides and dimethylsulfide were formed from 3-methylthiopropionate, a metabolite in the transamination pathway of methionine, during incubation with human and rat hepatocytes. An increase of the 3-methylthiopropionate concentration resulted in an increased formation of the products, up to a substrate concentration of 4.4 mM. Higher substrate levels resulted in a decreased methanethiol formation, probably due to poisoning of the system. However, in human hepatocytes the formation of dimethylsulfide increased up to a 3-methylthiopropionate concentration of 12.5 mM. The formation of methanethiol, dimethylsulfide and methanethiol-mixed disulfides from 3-methylthiopropionate in hepatocytes of both human and rat support the hypothesis that methanethiol can be formed from methionine via the transamination pathway.

Transamination of methionine in humans.

1. This study was designed to investigate the transamination pathway of methionine in humans. 2. Evidence is provided that methanethiol and its metabolites are formed via transamination of methionine. 3. Gas-liquid chromatography was used to measure serum and urinary transamination metabolites of methionine: 2-keto-4-methylthiobutyrate, 3-methylthiopropionate and methanethiol, and the metabolites of methanethiol, dimethylsulphide, protein-S-S-CH3 (a mixed disulphide of blood proteins and methanethiol) and X-S-S-CH3 (a mixed disulphide of methanethiol and another thiol with an unknown component X). 4. Methionine and the transamination intermediates were measured in 10 normal subjects, in six normal subjects after L-methionine loading (0.1 g/kg body weight) and in a male patient with hepatic methionine adenosyltransferase (EC 2.5.1.6) deficiency. 5. In the patient with methionine adenosyltransferase deficiency, at least 20% of methionine was degraded via transamination. In normal subjects transamination of methionine did exist but was quantitatively not important in methionine catabolism, not even after methionine loading. 6. The results of this study might be of importance for future studies on the role of methanethiol in hepatic encephalopathy.

Differences between premenopausal women and young men in the transamination pathway of methionine catabolism, and the protection against vascular disease.

Catabolism of methionine is supposed to proceed via two known pathways: transsulphuration and transamination. In 10 premenopausal women and 13 young men we measured methionine, the transsulphuration metabolite homocysteine, and the transamination metabolites 4-methylthio-2-oxo-butryate and methanethiol mixed disulphides in the fasting state as well as after oral administration of 0.1 g L-methionine kg-1 body weight. Both in the fasting state and after methionine loading the concentrations of homocysteine in serum were significantly lower in premenopausal women than in young men. Since there is evidence that even a moderate homocysteinaemia may be a risk factor in the development of vascular disease, the low homocysteine levels could be an additional factor contributing to the lower incidence of vascular disease in premenopausal women. After oral methionine these women showed significantly higher concentrations both in serum and urine of the transamination metabolites than the group of men. This higher methionine transamination in premenopausal women may contribute to keeping the homocysteine levels low and may therefore have an impact on the protection of these women against vascular disease.