Phenyl glyoxal in borate buffer specifically inactivates the NADPH-linked activity of yeast glutathione reductase. While NAD+ is ineffective, NADP+ prevents the enzyme from inactivation, and in the process, protects two arginine residues from glyoxalation. These two arginine residues presumably function as the recognition site for the anionic 2'-phosphate group of NADP+.