Binding of acrylamide with glutathione- S-transferases

Abstract

Introduct ion GST, a family of cytosolic enzymes, plays an important role in cellular biotransformation and elimination of toxic electrophiles by glutathione conjugation and subsequent excretion as mereapturic acid [1,2]. GST bind a broad range of substrate and non~substrate ligands and subsequently function both as catalytic proteins for cellular biotransformation and as an organic anion or receptor protein [ 3--7 ]. ACR (CH2CHCONH2) is an extensively used monomer in polymer industry and is a potent neurotoxin [8]. Exposure of humans and animals to ACR leads to a typical peripheral neuropathy in nervous system [ 8]. To date very little is known about the biotransforrnation of ACR [9]. Our recent studies have demonstrated that ACR reacts with glutathione both nonenzymically and enzymically. Enzymically both liver and brain GST catalyze the formation of S-conjugates and therefore acrylamide acts as substrate for GST (R. Dixit et al., pets. comm.). In view of the wide range of ligands (both substrate and non~substrate) that bind to GST [3--7], it was of interest to study interaction of ACR with GST. The present report summarises the observations which suggest that the conjugating enzyme may be identical with the protein which binds ACR.