Aldose reductase (AR) is a cytosolic monomeric enzyme that belongs to the aldo-keto reductase (AKR) superfamily. This superfamily includes more than 150 NAD(P)(H)-dependent oxidoreductases found in all prokaryotic and eukaryotic kingdoms, including yeast, plants, invertebrates, and vertebrates . The enzyme is known for its role in the polyol pathway, where it catalyzes the reduction of glucose to sorbitol .
Aldose reductase is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme that catalyzes the reduction of various aldehydes and ketones to their corresponding alcohols . The enzyme consists of 316 amino acid residues and weighs approximately 35,853 Da . The active site pocket of aldose reductase is relatively hydrophobic, lined by several aromatic and non-polar residues .
Aldose reductase has been extensively studied due to its involvement in diabetic complications . Under diabetic conditions, the enzyme converts excess glucose into sorbitol, which is then converted to fructose . This accumulation of sorbitol and fructose can lead to osmotic stress and contribute to various diabetic complications, such as diabetic retinopathy and nephropathy .
Aldose reductase is ubiquitously expressed in various human organs, including the kidney, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, and liver . However, AR-like proteins exhibit tissue-specific patterns of expression . For instance, certain isoforms are enriched in the adrenal gland, enterohepatic, and adipose tissues .
Beyond its role in detoxification, recent studies suggest that aldose reductase and its isoforms may have additional physiological functions . These enzymes are capable of modifying or generating signaling molecules, shifting their status from mere scavengers to important messengers . This has implications for their roles in glucido-lipidic metabolism and adipose tissue homeostasis .
Aldose reductase is involved in many oxidative stress diseases, cell signal transduction, and cell proliferation processes, including cardiovascular disorders, sepsis, and cancer . Inhibition of aldose reductase has been suggested as a therapeutic strategy to reduce inflammation associated with the activation of retinal microglia .