ELECTROSTATIC PROPERTIES OF GLUTATHIONE - A QUANTUM MOLECULAR STUDY

Glutathione (GSH) is the most abundant intracellular thiol. This tripe ptide, the gamma-L-glutamyl-L-cysteinylglycine, is present inside cell s as free sulfhydryl (reduced-form GSH) and in the oxidized-form GSSG, which is converted to GSH by the intracellular enzyme glutathione red uctase, in the presence of NADPH. GSH presents numerous functional act ivities in intermediate metabolism, biosynthesis of macromolecules, tr ansports, cancer therapy, and radioprotection. In all its multifunctio nal roles, GSH is in the globally monoanionic form GSH(-) and the thre e charged groups (the positive amino group and the two negative carbox ylate groups) are strongly involved with regard to the environment, pa rticularly, in the GSH-enzyme interactions. Therefore, the intrinsic e lectrostatic properties of GSH are the first step to the understanding of the molecular mechanism of these interactions. In our study, we pr esent electrostatic properties of GSH, versus Various allowed conforma tions, using ab initio computations. Charges distributions and molecul ar electrostatic potentials are discussed with regard to the involveme nt of GSH in its various functions. (C) 1993 John Wiley & Sons, Inc.