Aldose reductase (AR) is an enzyme that belongs to the aldo-keto reductase (AKR) superfamily. This superfamily includes more than 150 NAD(P)(H)-dependent oxidoreductases found across various prokaryotic and eukaryotic organisms, including yeast, plants, invertebrates, and vertebrates . In humans, aldose reductase is encoded by the gene AKR1B1 .
Aldose reductase is a cytosolic NADPH-dependent oxidoreductase that catalyzes the reduction of a wide range of aldehydes and carbonyls, including monosaccharides . The enzyme is primarily known for catalyzing the reduction of glucose to sorbitol, which is the first step in the polyol pathway of glucose metabolism . This pathway is significant because it converts glucose to fructose, utilizing NADPH and producing NADH in the process .
The reaction catalyzed by aldose reductase can be summarized as follows:
Aldose reductase plays a crucial role in various physiological processes. For instance, the sorbitol produced in the polyol pathway is important for the function of several organs . In the seminal vesicles, fructose produced from sorbitol is utilized by sperm cells . In the liver, fructose can be used as an energy source for glycolysis and gluconeogenesis . Additionally, aldose reductase is present in the lens, retina, Schwann cells of peripheral nerves, placenta, and red blood cells .
Aldose reductase has been extensively studied due to its role in diabetic complications . The enzyme’s activity leads to the accumulation of sorbitol in tissues, which can cause osmotic stress and contribute to the development of diabetic neuropathy, retinopathy, and cataracts . As a result, aldose reductase inhibitors have been explored as potential therapeutic agents for managing diabetic complications .
Human recombinant aldose reductase is produced using recombinant DNA technology, which involves inserting the human AKR1B1 gene into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities . This recombinant enzyme is used in various research applications to study its structure, function, and role in disease processes .