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E. P. Jeffreys, and R. C. Warner, J. Biol. Chem. 117, 237 (1937). 3 A. Szent-GyOrgyi,Biochem. J. 22, 1387 (1928). 4 E. M. Crook, Biochem. J. 35, 226 (1941). 5 M. A. Hossain and K. Asada, Plant Cell Physiol. 25, 85 (1984). 6 R. L. Stahl, L. F. Liebes, and R. Silber, this series, Vol. 122, p. 10. 7 R. E. Hughes, Nature ( L o n d o n ) 203, 1068 (1964). s L. Christine, G. Thomson, B. Iggo, A. C. Brownie, and C. P. Stewart, Clin. Chim. Acta 1, 557 (1956). 9 A. Holmgren, Proc. Natl. Acad. Sci. A. 73, 2275 (1976).

Acad. A. $9, 164 (1968). s For a review, see A. Meister, Chemtracts: Biochem. Mol. Biol. 3, 75 (1992). 9 A. Meister, in "Glutathione Centennial: Molecular Perspectivesand Clinical Implications," (N. Taniguchi, T. Higashi, Y. Sakamoto, and A. ), Chap. 1, p. 3. Academic Press, New York, 1989. 10j. M. Manning, S. Moore, W. B. Rowe, and A. Meister, Biochemistry 8, 2681 (1969). [3] GLUTATHIONE BIOSYNTHESIS AND ITS INHIBITION 29 mine synthetase, n Administration of methionine sulfoximine to experimental animals leads to a decrease in the synthesis of glutamine and also that of GSH.

254, 9627 (1979). 25A. L. Ibbetson and R. B. Freedman, Biochem. J. 159, 377 (1976). 38 GLUTATHIONE 15] iodoacetamide and other alkylating agents (data not shown) and by platinum complexes. 26 By using site-directed mutagenesis techniques, the essential amino acids at the catalytic center of porcine thioltransferase (dehydroascorbate reductase) were determinedY Seven mutant cDNAs were constructed, subcloned in plasmid pKK233-2, and transfected into E. coli JM105. The proteins were induced by isopropyl-l-thio-/3-D-galactopyranoside treatment at high yields.

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