Aldose reductase

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Ribbon diagram of human aldose reductase in complex with NADP+, citrate, and IDD594, a small molecule inhibitor. From PDB 1us0.

Aldose reductase (or aldehyde reductase) is an enzyme in carbohydrate metabolism that converts glucose to sorbitol.

The enzyme can be inhibited by aldose reductase inhibitors.

[edit] Reactions

Specific reactions catalyzed by this enzyme include:

• glucose + NADPH + H⁺--> sorbitol + NADP⁺

• galactose + NADPH + H⁺--> galactitol + NADP⁺

[edit] Role in diabetes

Glucose concentrations are often elevated in diabetics and aldose reductase has long been believed to be responsible for diabetic complications involving a number of organs. Many aldose reductase inhibitors have been developed as drug candidates but virtually all have failed although some are commercially available in several countries.

[edit] Function

The aldose reductase reaction, in particular the sorbitol produced, is important for the function of various organs in the body. For example, it is generally 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. The main pathway from glucose to fructose (glycolysis) 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.

[edit] Structure

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

[edit] References

• Denise R., PhD. Ferrier (2005). Lippincott's Illustrated Reviews: Biochemistry (Lippincott's Illustrated Reviews). Hagerstown, MD: Lippincott Williams & Wilkins. p. 319. ISBN 0-7817-2265-9. 

[edit] References

• IUBMB entry for 1.1.1.21
• BRENDA references for 1.1.1.21
• PubMed references for 1.1.1.21
• PubMed Central references for 1.1.1.21
• Google Scholar references for 1.1.1.21
• AKR1A1, AKR1B1

[edit] External links

• IUBMB entry for 1.1.1.21
• KEGG entry for 1.1.1.21
• BRENDA entry for 1.1.1.21
• NiceZyme view of 1.1.1.21
• EC2PDB: PDB structures for 1.1.1.21
• PRIAM entry for 1.1.1.21
• PUMA2 entry for 1.1.1.21
• IntEnz: Integrated Enzyme entry for 1.1.1.21
• MetaCyc entry for 1.1.1.21
• Atomic-resolution structures of enzymes belonging to this class