title: Five decades with glutathione and the GSTome.
abstract: Uncle Folke inspired me to become a biochemist by demonstrating electrophoresis experiments on butterfly hemolymph in his kitchen. Glutathione became the subject for my undergraduate project in 1964 and has remained a focal point in my research owing to its multifarious roles in the cell. Since the 1960s, the multiple forms of glutathione transferase (GST), the GSTome, were isolated and characterized, some of which were discovered in our laboratory. Products of oxidative processes were found to be natural GST substrates. Examples of toxic compounds against which particular GSTs provide protection include 4-hydroxynonenal and ortho-quinones, with possible links to the etiology of Alzheimer and Parkinson diseases and other degenerative conditions. The role of thioltransferase and glutathione reductase in the cellular reduction of disulfides and other oxidized forms of thiols was clarified. Glyoxalase I catalyzes still another glutathione-dependent detoxication reaction. The unusual steady-state kinetics of this zinc-containing enzyme initiated model discrimination by regression analysis. Functional properties of the enzymes have been altered by stochastic mutations based on DNA shuffling and rationally tailored by structure-based redesign. We found it useful to represent promiscuous enzymes by vectors or points in multidimensional substrate-activity space and visualize them by multivariate analysis. Adopting the concept "molecular quasi-species," we describe clusters of functionally related enzyme variants that may emerge in natural as well as directed evolution.
authors.affiliation: Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden. bengt.mannervik@kemi.uu.se
authors.forename: Bengt
authors.initials: B
authors.lastname: Mannervik
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000266:history*; D004734:Energy Metabolism / Q000502:physiology; D005180:Faculty, Medical / Q000266:history*; D005978:Glutathione / Q000266:history* / Q000378:metabolism; D005982:Glutathione Transferase / Q000266:history* / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000266:history* / Q000378:metabolism; D013548:Sweden
chemical_list: D005982:Glutathione Transferase; D007791:Lactoylglutathione Lyase; D005978:Glutathione