Aldose reductase (EC 1.1.1.21) from human brain has been purified to apparent homogeneity. The enzyme catalyzes the NADPH-dependent reduction of several physiological and xenobiotic aldehydes. Isocorticosteroids, e.g. isocortisol and isocorticosterone, are the best substrates (K, < 1 pm), followed by aromatic and arylalkylaldehydes, including biogenic aldehydes ( K , = 3 -15 pM). The activity tcwards aldoses is highest with glyceraldehyde ( K , = 25 pM) and decreases with increasing number of carbon atoms of the sugar.Flavonoids, e.g. quercetin and rutin, inhibit aldose reductase (I& = 2-5 pM). Sulfate ions, on the other hand, stimulate the enzyme activity. Thiol-modifying reagents, e.g. 4-hydroxymercuribenzoate and iodoacetate, cause a time-dependent inactivation.Aldose reductase consists of a single polypeptide chain with a molecular weight of 38000 and an isoelectric point of 5.9. In the presence of thiol reagents the isoelectric point is shifted to 5.1.Antibodies against aldose reductase do not cross-react with other carbonyl reductases, Nevertheless, the comparison of structural and enzymic properties of aldose reductase with those of other carbonyl reductases suggests a relationship between aldose reductase and aldehyde reductase (EC 1.1.1.2).Aldose reductase (alditol : NADP' 1-oxidoreductase) catalyzes the conversion of aldoses and a number of other aldehydes to the corresponding alcohol metabolites. It is one of several cytosolic, monomeric, NADPH-dependent aldehyde and ketone reductases of wide substrate specificity that are generally referred to as carbonyl reductases [I 1.Aldose reductase together with sorbitol dehydrogenase constitutes the polyol pathway, a minor route of carbohydrate metabolism converting glucose to fructose [2]. Under normal conditions there is little flux through this pathway. However, in diabetic hyperglycaemic conditions the flux increases dramatically, leading to elevated cellular concentrations of the intermediate sorbitol, which in turn cause a hyperosmotic effect and swelling of the cell. This process has been shown to initiate cataract formation in diabetic animals [3], and it may also play a role in the pathogenesis of other diabetic complications, such as neuropathy [4].In addition to its function as one of the enzymes of the polyol pathway, aldose reductase appears to play a role in the metabolism of the biogenic amines. In the nervous system, biogenic amines, which bear a hydroxyl group adjacent to the amine function, e.g. noradrenaline, are catabolized to the glycol products, whereas the amines lacking the hydroxyl group, such as serotonin and dopamine, are mainly converted to the acid metabolites [5]. The bifurcation into an oxidative and reductive pathway results from the action of specific dehydrogenases and reductases on the aldehyde metabolites derived from the amines by monoamine -oxidase-catalyzed Abbreviations. Isocortisol, 1 1 p,17fl,20a/fl-trihydroxy-3-oxo-pregn-4-en-23-al; isocorticosterone, 11~,20cc/~-dihydroxy-3-oxo-pregn-4-en-