The Nature and Function of Aldehyde Reductases from Rat Brain

Abstract

Aldehyde reductases (EC 1.1.1.2) appear to play a number of distinct functions in cellular metabolism (Tipton et al., 1977). In neuronal tissue, they predominantly function in the reduction of aldehydes generated by oxidative deamination of monoamines or transamination of γ-aminobutyric acid (GABA). They may also play a role in the metabolism of aldoses and have been implicated in drug metabolism in liver (Turner and Hick, 1976; Bachur, 1976). In most tissues examined there exist several aldehyde reductases which may differ in subcellular location, inhibitor sensitivity and substrate specificity (Turner and Tipton, 1972a; Ris and von Wartburg, 1973; Anderson et al., 1976). The major reductase in all tissues (AR1 or “high-K_m”) is characterized by a cytosolic location, a specific requirement for NADPH and a low specificity for aldehyde substrates. A feature of this enzyme is that it exhibits a substantial preference for 2-hydroxy aldehydes (Turner and Tipton, 1972b; Wermuth and Münch, 1979). Rat brain and other tissues contain at least one other aldehyde reductase (AR2 or “low-K_m”) that is similar to or identical with aldose reductase (EC 1.1.1.21) (Turner and Tipton, 1972b). This latter enzyme has been implicated in some of the secondary effects of diabetes such as cataract formation (Gabbay and O’Sullivan, 1968). The relative contributions of these two reductases to the physiological metabolism of aldehydes is at present unclear. Some species may contain additional isoenzymes of aldehyde reductase (Ris and von Wartburg, 1973).