Glutathione reductase specificity

Henderson, G. B., Murgolo, N.J., Kuriyan, J., Osapay, K., Kominos, D., Berry, A., Scrutton, N. S., Hinchlifife, N. W., Perham, R. N. Cerami, A. (1991). Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction. Proceedings of the National Academy of Sciences USA, 88, 8769-73. 

Perham, R. N., Scrutton, N.S. Berry, A. (1991)- New enzymes for old redesigning the coenzyme and substrate specificities of glutathione reductase. Bioessays, 13, 515-25. 

The third system is that of thioltransferase, which may not be distinct from glutaredoxin in some tissues. The thioltransferase system is composed of thioltransferase, GSH, glutathione reductase and NADPH. All thioltransferases which have been found in mammalian cells have molecular weights which are close to 11 KDa. Sub-millimolar concentrations of either cystamine or cystine inactivate GST-IT from human placenta with concomitant formation of enzyme mixed-disulfides [282]. Thioltransferase from human placenta specifically reactivates GST-IT in the presence of 10-100 pM GSH while thioredoxin is inactive [282], Thioltransferase-mediated cleavage of mixed disulfides was also shown to restore enzyme activities in phosphofructokinase [283] and pyruvate kinase [284]. 

The specificity of these enzymes toward their disulfide substrates is quite remarkable There is virtually no cross-reactivity. Since it is quite difficult to separate glutathione reductase from thioredoxin reductase it... 

The three enzymes are quite specific for their respective pyridine nucleotide substrates. Under conditions normally used for assay, lipoamide dehydrogenase is less than % as active with NADPH as with NADH IS) and thioredoxin reductase is less than 1% as active with NADH as with NADPH 36, Sff). Lipoamide dehydrogenase can transfer electrons to a number of NAD analogs 37). Yeast glutathione reductase is quite specific for NADPH 60), but the erythrocyte enzyme is 20% as active with NADH as with NADPH under the conditions of the standard assay 30,40,61). 

The specificity of glutathione reductase toward its disulfide substrate was emphasized in Section II,A, since there is virtually no reactivity with the substrates of the other pyridine nucleotide-disulfide oxidoreductases. Other authors have emphasized the lack of specificity of this enzyme since it can catalyze the reduction of a variety of mixed disulfides provided that glutathione or y-glutamylcysteine comprises one-half (IP5, 21%) Table IV summarizes these (39, 226-231). It is important to distin-... 

Glutathione reductase amino acid composition, 102,104,105 cystine residues, 104 kinetic studies, 138-141 mechanism, 94, 97-98,134 metabolic functions, 129-133 reaction catalyzed, 92 reduction of, 112, 113 specificity of, 92-93 coenzymes and, 94 thiol groups, 141-142 two-electron-reduced enzyme, properties, 133-138... 

Prentice AM and Bates CJ (1981a) A biochemical evaluation of the erythrocyte glutathione reductase (EC 1.6.4.2) test for riboflavin status. 1. Rate and specificity of response in acute deficiency. British Journal of Nutrition 45,37-52. 

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