title: New insights into the metabolism of organomercury compounds: mercury-containing cysteine S-conjugates are substrates of human glutamine transaminase K and potent inactivators of cystathionine γ-lyase.
abstract: Anthropogenic practices and recycling in the environment through natural processes result in release of potentially harmful levels of mercury into the biosphere. Mercury, especially organic forms, accumulates in the food chain. Mercury reacts readily with sulfur-containing compounds and often exists as a thiol S-conjugate, such as the l-cysteine (Cys)-S-conjugate of methylmercury (CH(3)Hg-S-Cys) or inorganic mercury (Cys-S-Hg-S-Cys). These S-conjugates are structurally similar to l-methionine and l-cystine/l-cystathionine, respectively. Bovine and rat glutamine transaminase K (GTK) catalyze transamination of sulfur-containing amino acids. Recombinant human GTK (rhGTK) has a relatively open catalytic active site, and we report here that this enzyme, like the rat and bovine enzymes, can also utilize sulfur-containing l-amino acids, including l-methionine, l-cystine, and l-cystathionine as substrates. The current study extends this list to include mercuric S-conjugates, and shows that CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are substrates and reversible inhibitors of rhGTK. The homocysteine S-conjugates, Hcy-S-Hg-S-Hcy and CH(3)Hg-S-Hcy, are also inhibitors. Finally, we show that HgCl(2), CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are potent irreversible inhibitors of rat cystathionine γ-lyase. The present study broadens our knowledge of the biochemistry of mercury compounds by showing that Cys S-conjugates of mercury interact with enzymes that catalyze transformations of biologically important sulfur-containing amino acids.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA.
authors.forename: Christy C
authors.initials: CC
authors.lastname: Bridges
authors.forename: Boris F
authors.initials: BF
authors.lastname: Krasnikov
authors.forename: Lucy
authors.initials: L
authors.lastname: Joshee
authors.forename: John T
authors.initials: JT
authors.lastname: Pinto
authors.forename: André
authors.initials: A
authors.lastname: Hallen
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.forename: Rudolfs K
authors.initials: RK
authors.lastname: Zalups
authors.forename: Arthur J L
authors.initials: AJ
authors.lastname: Cooper
mesh_terms: D000603:Amino Acids, Sulfur / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D003553:Cystine / Q000378:metabolism*; D006801:Humans; D008190:Lyases / Q000378:metabolism*; D008627:Mercuric Chloride / Q000378:metabolism; D008767:Methylmercury Compounds / Q000378:metabolism; D008958:Models, Molecular; D009941:Organomercury Compounds / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism*
chemical_list: C494607:2-amino-3-(2-amino-2-carboxyethylsulfanyl-mercuricsulfanyl)-propionic acid; D000603:Amino Acids, Sulfur; D008767:Methylmercury Compounds; D009941:Organomercury Compounds; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D003553:Cystine; D008627:Mercuric Chloride; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; D008190:Lyases; D003542:Cystathionine gamma-Lyase; D003545:Cysteine
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