The DOI matches its Crossref record; 113 of the 113 references it cites were found in a registry or an index.
The Enzymes of Glutathione Synthesis: γ‐Glutamylcysteine Synthetase
Abstract
The metabolite glutathione fulfills many important and chemically complex roles in protecting cellular components from the deleterious effects of toxic species. GSH combines with hydroxyl radical, peroxynitrite, and hydroperoxides, as well as reactive electrophiles, including activated phosphoramide mustard. This thiol-containing reductant also maintains so-called thiol-enzymes in their catalytically active form, and maintains vitamins C and E in their biologically active forms. The key step in glutathione synthesis, namely the ATP-dependent synthesis of gamma-glutamylcysteine, is the topic of this review. Details are presented on (a) the enzyme's purification and protein chemistry, (b) the successful cDNA cloning, and characterization of the genes responsible for the biosynthesis of this enzyme. After considering aspects of the role of overexpression of this synthetase in terms of cancer chemotherapy, attention is focused on post-translational regulation. The remainder of the review deals with the catalytic mechanism (including substrate specificity, reactions catalyzed, steady-state kinetics, and chemical mechanism) as well as the inhibition of the enzyme (via feedback inhibition, reaction with S-alkyl homocysteine sulfoximine inhibitors, the clinical use of buthionine sulfoximine with cancer patients, and inactivation by cystamine, chloroketones, and various nitric oxide donors).
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Cites
Meister, A., & Anderson, M. E. (1983) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.52.070183.003431 · Cited by 5,680
Antioxidant and redox regulation of gene transcription
Sen, C. K., & Packer, L. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.7.8635688 · Cited by 1,981
Glutathione Transferases—Structure and Catalytic Activit
Mannervik, B., Helena Danielson, U., & Ketterer, B. (1988) · Critical Reviews in Biochemistry · doi:10.3109/10409238809088226 · Cited by 1,756
Griffith, O. W., & Meister, A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35980-5 · Cited by 1,683
Self-citationStructure, Catalytic Mechanism, and Evolution of the Glutathione Transferases
Armstrong, R. N. (1997) · Chemical Research in Toxicology · doi:10.1021/tx960072x · Cited by 1,143
Godwin, A. K., Meister, A., O'Dwyer, P. J., Huang, C. S., Hamilton, T. C., & Anderson, M. E. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.3070 · Cited by 925
Meister, A. (1991) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(91)90076-x · Cited by 907
ROLE OF REVERSIBLE OXIDATION-REDUCTION OF ENZYME THIOLS-DISULFIDES IN METABOLIC REGULATION
Ziegler, D. M. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.001513 · Cited by 836
METABOLISM AND FUNCTIONS OF TRYPANOTHIONE IN THE KINETOPLASTIDA
Fairlamb, A. H., & Cerami, A. (1992) · Annual Review of Microbiology · doi:10.1146/annurev.mi.46.100192.003403 · Cited by 768
Molecular and Cellular Aspects of Thiol–Disulfide Exchange
Gilbert, H. F. (1990) · Advances in Enzymology - and Related Areas of Molecular Biology · doi:10.1002/9780470123096.ch2 · Cited by 758
Cited by
Glutathione in Cancer Biology and Therapy
Estrela, J. M., Ortega, A., & Obrador, E. (2006) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360500523878 · Cited by 1,041
Kode, A., Rajendrasozhan, S., Caito, S., Yang, S.-R., Megson, I. L., & Rahman, I. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00361.2007 · Cited by 447
Franklin, C. C., Backos, D. S., Mohar, I., White, C. C., Forman, H. J., & Kavanagh, T. J. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.009 · Cited by 438
Maya, J. D., Cassels, B. K., Iturriaga-Vásquez, P., Ferreira, J., Faúndez, M., Galanti, N., Ferreira, A., & Morello, A. (2007) · Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2006.03.004 · Cited by 359
Laminar Flow Induction of Antioxidant Response Element-mediated Genes in Endothelial Cells
Chen, X.-L., Varner, S. E., Rao, A. S., Grey, J. Y., Thomas, S., Cook, C. K., Wasserman, M. A., Medford, R. M., Jaiswal, A. K., & Kunsch, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m203161200 · Cited by 333
Metadata
- Authors
- Griffith, O. W., & Mulcahy, R. T.
- Venue
- Advances in Enzymology - and Related Areas of Molecular Biology
- Publisher
- Wiley
- Published
- 1999-01
- Volume
- 73
- Pages
- 209-267
- ISSN
- 0065-258X (ISSN-L)
- 1934-4694
- OpenAlex
- W1898716493
- Cited by
- 253
- References
- 113
- Type
- other
- Language
- en
- Open access
- closed
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