Electrostatic properties of glutathione: A quantum molecular study

Abstract

Glutathione (GSH) is the most abundant intracellular thiol. This tripeptide, the y-L-glutamyl-Lcysteinylglycine, is present inside cells as free sulfhydryl (reduced-form GSH) and in the oxidized-form GSSG, which is converted to GSH by the intracellular enzyme glutathione reductase, in the presence of NADPH. GSH presents numerous functional activities in intermediate metabolism, biosynthesis of macromolecules, transports, cancer therapy, and radioprotection. In all its multifunctional roles, GSH is in the globally monoanionic form GSH-and the three charged groups (the positive amino group and the two negative carboxylate groups) are strongly involved with regard to the environment, particularly, in the GSH-enzyme interactions. Therefore, the intrinsic electrostatic properties of GSH are the first step to the understanding of the molecular mechanism ofthese interactions. In our study, we present electrostatic properties of GSH, versus various allowed conformations, using ab inifio computations. Charges distributions and molecular electrostatic potentials are discussed with regard to the involvement of GSH in its various functions.

Molecular Electrostatics

“…Figures were produced with the SYBYL software275 using atomic monopoles after Gasteiger and Marsili.274 and several other problems of pharmacological interest. [261][262][263][264][265][266][267] The MEP is used also in the CoMFA analysis268-270 that became recently very popular in structure-based molecular design. It was also pos-sible to design a transition-state analogue of nucleoside hydrolase on the basis of the MEP.…”

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

“…However, most of the intracellular GSH is removed by centrifugation during the preparation of the microsomes so that their GSH concentration is very low. To mimic physiological conditions, GSH as well as GST were added in appropriate near-physiological concentrations [26,27]. The occurrence of other major phase II reactions was already excluded (cf.…”

“…(16,17,19,20,21,22), degradation products of the former(18,26,27,32), water conjugates (33, 34), a methylated water conjugate(35) and combinations thereof (23, 24, 25, 28, 29, 30, 31). Furthermore, hydroxides (36, 37), 1 water conjugated hydroxide(38) and 1 hydrogenated metabolite (39 = DHac) were formed.…”