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Aldose reductase
Aldose reductase 1us0.png
Ribbon diagram of human aldose reductase in complex with NADP+, citrate, and IDD594, a small molecule inhibitor. From PDB 1us0.
Identifiers
EC number 1.1.1.21
CAS number 9028-31-3
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures

Aldose reductase (or aldehyde reductase) is an enzyme in carbohydrate metabolism that converts glucose to sorbitol.[1]

Contents

Reactions

Specific reactions catalyzed by this enzyme include:

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:

Aldose reductase is also present in the lens, retina, Schwann cells of peripheral nerves, placenta and red blood cells.

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 such as epalrestat are commercially available in several countries. Additional reductase inhibitors such as ranirestat, ponalrestat, rinalrestat, risarestat, rmirestat, sorbinil, and [[berberine[2] are currently in clinical trials.[3]

See also

References

  1. ^ Petrash JM (April 2004). "All in the family: aldose reductase and closely related aldo-keto reductases". Cell. Mol. Life Sci. 61 (7-8): 737–49. doi:10.1007/s00018-003-3402-3. PMID 15094999.  
  2. ^ Wu LY, Ma ZM, Fan XL, Zhao T, Liu ZH, Huang X, Li MM, Xiong L, Zhang K, Zhu LL, Fan M (November 2009). "The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells". Cell Stress Chaperones. doi:10.1007/s12192-009-0153-6. PMID 19902381.  
  3. ^ Schemmel KE, Padiyara RS, D'Souza JJ (September 2009). "Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review". J. Diabetes Complicat.. doi:10.1016/j.jdiacomp.2009.07.005. PMID 19748287.  

Further reading

  • 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.  
  • Attwood MA, Doughty CC (December 1974). "Purification and properties of calf liver aldose reductase". Biochim. Biophys. Acta 370 (2): 358–68. PMID 4216364.  
  • Boghosian RA, McGuinness ET (April 1979). "Affinity purification and properties of porcine brain aldose reductase". Biochim. Biophys. Acta 567 (2): 278–86. PMID 36151.  
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