The mechanism of biliary excretion of methyl mercury: studies with methylthiols.
The S-methylated derivatives of N-acetylpenicillamine, thiola and cysteine as well as methyl iodide decreased biliary excretion of methyl mercury markedly. Excretion of sulfhydryl in bile was not influenced by S-methyl-cysteine, S-methylthiola, S-methyl-N-acetylpenicillamine or a low dose of methyliodide (0.5 mmol/kg body weight). This seems to indicate that coupling of methyl mercury to glutathione in the liver before biliary excretion is a glutathione S-transferase dependent reaction. It also indicates that the methylthiols tested, or metabolites of these compounds are likely to be inhibitors of S-transferase. The effect of S-methylcysteine and low doses of methyl iodide probably reflects glutathione S-transferase inhibition as both compounds are metabolized to the S-transferase inhibitor S-methylglutathione in the liver. A higher dose of methyl iodide (1 mmol/kg body weight) seems to deplete the liver of reduced glutathione through S-methylation as illustrated by decreased biliary excretion of sulfhydryl. S-methylthiola and S-methyl-N-acetylpenicillamine are metabolized in the liver to unknown components which are excreted in bile. Whether S-methylthiola and S-methyl-N-acetylpenicillamine are inhibitors of S-transferase themselves or cause inhibition through metabolites cannot be stated from the present investigation.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D006847:Hydrocarbons, Iodinated / Q000494:pharmacology; D008297:Male; D008767:Methylmercury Compounds / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D008625:Tiopronin / Q000031:analogs & derivatives / Q000378:metabolism
D006847:Hydrocarbons, Iodinated; D008767:Methylmercury Compounds; C039022:S-methyl-N-acetylpenicillamine; C039021:S-methylthiola; C008425:S-methylcysteine; D008625:Tiopronin; C014055:methyl iodide; D010396:Penicillamine; D003545:Cysteine