Aldose reductase

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Aldose reductase is an enzyme in carbohydrate metabolism that converts glucose to its sugar alcohol form, sorbitol, using NADPH as the reducing agent. The reaction equation is glucose + NADPH + [[H⁺]]--> sorbitol + [[NADP⁺]]. Glucose concentrations are often elevated in diabetics and this enzyme has long been believed to be responsible for diabetic complications involving a number of organs. Many inhibitors have been developed as drug candidates but virtually all have failed although some are commercially available in several countries. This reaction, in particular the sorbitol produced, is important for the function of various organs in the body. Generally it is used as the first step in a synthesis of fructose from glucose; the second step is the oxidation of sorbitol to fructose catalyzed by sorbitol dehydrogenase. There is another pathway from glucose to fructose that involves phosphorylation of glucose by hexokinase to form glucose 6-phosphate, followed by isomerization to fructose 6-phosphate and hydrolysis of the phosphate, but the sorbitol pathway is useful because it does not require the input of energy in the form of ATP:

Seminal vesicles: Fructose produced from sorbitol is used by the sperm cells.
Liver: Fructose produced from sorbitol can be used as an energy source for glycolysis and glyconeogenesis.

Aldose reductase is also present in the lens, retina, Schwann cells of peripheral nerves, placenta and red blood cells. The enzyme can be inhibited by aldose reductase inhibitors.

The structure of the enzyme, bound to its cofactor NADPH, can be found at [1].