Comparison of the effects of buthioninesulfoximine and phorone on the metabolism of sulfur-containing amino acids in rat liver.
Alterations in hepatic transsulfuration reactions were determined in rats treated with a glutathione-depleting agent. A dose of l-buthionine-(S,R)-sulfoximine decreased hepatic methionine, cysteine, S-adenosylmethionine, and glutathione levels rapidly. Methionine adenosyltransferase and gamma-glutamylcysteine lygase activities were decreased transiently, but significantly. The activity of cysteine dioxygenase was increased, resulting in an elevation of hypotaurine and taurine concentrations. Administration of phorone reduced hepatic glutathione and cysteine similarly, but S-adenosylmethionine concentrations were elevated for as long as 72h. Hepatic methionine adenosyltransferase, cystathionine beta-synthase, cystathionine gamma-lyase, and gamma-glutamylcysteine lygase activities were all increased but cysteine dioxygenase activity and taurine generation were markedly depressed. The results show that a decrease in hepatic GSH induces profound changes in sulfur amino acid metabolomics, which would subsequently influence various cellular processes. It is suggested that the change in hepatic levels of sulfur-containing substances and its physiological significance should be considered when a glutathione-depleting agent is utilized in biological experiments.
Jung
Young S
YS
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
Kim
Sun J
SJ
Kwon
Do Y
DY
Kim
Young C
YC
D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D050558:Cysteine Dioxygenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000378:metabolism
D000603:Amino Acids, Sulfur; D007659:Ketones; D019328:Buthionine Sulfoximine; D012436:S-Adenosylmethionine; C018637:phorone; D050558:Cysteine Dioxygenase; D008716:Methionine Adenosyltransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005981:Glutathione Synthase; D005978:Glutathione