Conference paper

Appeared in: Flavins and flavoproteins 1990

Editor list: Curti, B; Ronchi, S; Zanetti, G

Publication year: 1990

Pages: 847-850

ISBN: 0-89925-666-X

eISBN: 978-3-11-085542-5

DOI Link: https://doi.org/10.1515/9783110855425-164

Conference: 10th International Symposium on Flavins and Flavoproteins

Abstract: 

As indicated by experimenta naturae (riboflavin deficiency, glucose-6-phosphate dehydrogenase deficiency) an impaired activity of the erythrocytic flavoenzyme glutathione reductase (GR) protects from malaria. Since this antioxidant protein, catalyzing the reaction NADPH + H+ + GSSG NADP+ + 2GSH (EC 1.6.4.2), is well known it is considered as a target molecule for systematic drug design (1). BCNU (carmustine) is a clinically used cytostatic agent which also has antimalarial activity (2). This compound inhibits the 2-electron-reduced form (EH2) of glutathione reductase by carbamoylating Cys58, one of the active site thiols (3); the oxidized form (E) containing Cys58-Cys63 as a disulfide is not affected by BCNU. The effect of BCNU on FAD-free apoglutathione reductase has not yet been investigated although the apoenzyme can be the predominant form of erythrocyte GR in malaria-afflicted countries where riboflavin deficiency is widespread (4). A prevalence of apoGR is assumed to mitigate the course of tropical malaria (4); on the other hand a malaria therapy based on GR-inhibitors would be inefficient if the apoenzyme - being potential active holoenzyme - cannot be modified by substances like BCNU and its less toxic derivatives.

Harvard Citation style: Becker, K., Schöllhammer, T. and Schirmer, R. (1990) Binding of FAD to BCNU-treated apoglutathione reductase, in Curti, B., Ronchi, S. and Zanetti, G. (eds.) Flavins and flavoproteins 1990. Berlin: de Gruyter. pp. 847-850. https://doi.org/10.1515/9783110855425-164

APA Citation style: Becker, K., Schöllhammer, T., & Schirmer, R. (1990). Binding of FAD to BCNU-treated apoglutathione reductase. In Curti, B., Ronchi, S., & Zanetti, G. (Eds.), Flavins and flavoproteins 1990. (pp. 847-850). de Gruyter. https://doi.org/10.1515/9783110855425-164