Cys298 is responsible for reversible thiol-induced variation in aldose reductase activity.

Abstract

Aldose reductase (EC 1.1.1.21) has been purified to apparent homogeneity from a variety of tissues including placenta, brain, nerves, kidney, muscle and lens. Multiple molecular forms of aldose reductase have been claimed to be isolated from bovine lens (Jedziniak et al, 1971) and bovine kidney (Gabbay et al 1974). These forms were subsequently described by some authors whereas others found a single form only (for a review see Wermuth, 1985). Conversion by a reducing agent (ß-mercaptoethanol) of one form to a more acidic but activity-retaining form was reported by Wermuth et al (1982), and differential susceptibility to inhibition of different enzyme forms was first described by Maragoudakis et al (1984). Nonlinear kinetics were often attributed to the presence of multiple forms. Thus, two kinetically distinct forms of human erythrocyte aldose reductase were postulated (Srivastava et al 1985) and the presence of bovine aldose reductase oxidized by oxygen radical generating systems was suggested as a possible cause for the nonlinear kinetics (Del Corso et al, 1987). More recently, data seem to firmly establish the existence of different forms of aldose reductase: “activated” and “unactivated” forms were isolated from bovine kidney (Grimshaw (1990) and their persistent peculiar kinetic behavior was then essentially rationalized (Grimshaw, 1991, Grimshaw et al 1990, Kubiseski et al, 1992). Recent advances in molecular biology led to the in vitro expression of rat lens aldose reductase (Old et al 1990) and human aldose reductase (Grundmann et al 1990, Carper et al 1990, Nishimura et al 1990, Bohren et al 1991). Multiple molecular forms of recombinant aldose reductase have so far not been reported with the exception of some charge heterogeneity that is evident upon isoelectric focusing (Bohren et al. 1991).