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IN VIVO INHIBITION OF γ‐GLUTAMYLCYSTEINE SYNTHETASE BY l ‐METHIONINE‐RS‐SULFOXIMINE; INFLUENCE ON INTERMEDIATES OF THE γ‐GLUTAMYL CYCLE
Author(s) -
Orlowski Marian,
Wilk S.
Publication year - 1975
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1975.tb04374.x
Subject(s) - in vivo , glutathione , convulsant , methionine , enzyme , glutathione synthetase , biochemistry , kidney , metabolism , chemistry , biology , amino acid , endocrinology , receptor , microbiology and biotechnology
—The inhibition of γ‐glutamylcysteine synthetase and its influence on the concentration of intermediates associated with the metabolism of glutathione was studied in mice receiving methionine sulfoximine, a convulsant agent. The activity of the enzyme decreased significantly in the liver and kidney 1‐4 h after administration of methionine sulfoximine; the activity of the enzyme in the brain was unchanged after 1 and 2 h but decreased significantly after 4 h. There was a rapid and sharp decrease in the concentration of glutathione in the kidney and a slower decrease in the liver. Brain glutathione concentrations were unaffected. Methionine sulfoximine in vivo , inhibited the synthesis of l ‐γ‐glutamyl‐ l ‐α‐aminobutyrate after administration of l ‐α‐aminobutyrate, a reaction catalyzed by γ‐glutamylcysteine synthetase. The inhibitor also lowered the concentration of pyrrolidone carboxylate in mouse tissues and prevented the accumulation of this intermediate after administration of l ‐α‐aminobutyrate. The results show that methionine sulfoximine in vivo affects the metabolism of glutathione and that this action may contribute to its convulsive properties.