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Gene Review

AKR1B1  -  aldo-keto reductase family 1, member B1...

Homo sapiens

Synonyms: ADR, ALDR1, ALR2, AR, Aldehyde reductase, ...
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Disease relevance of AKR1B1


Psychiatry related information on AKR1B1

  • In addition to polyol synthesis, aldose reductase may have multiple other activities that intersect with signal processing and oxidative defense mechanisms [3].
  • Results from both dose-response and time-response studies strongly suggest a functional role for ADR in IL 2 mediated T cell growth [4].
  • The effects of dexmedetomidine, a subtype-nonselective alpha 2-AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the alpha 2C-AR gene and in their controls, but the hypothermic effect of the alpha 2-AR agonist was significantly attenuated by the receptor gene inactivation [5].
  • Excessive daytime sleepiness, which had occurred in the cases as an H1-antihistamine-induced ADR, was assessed by the Epworth sleepiness scale (ESS), and an ESS score >/=12 was considered hypersomnia [6].
  • Erythrocyte aldose reductase correlates with erectile dysfunction in diabetic patients [7].

High impact information on AKR1B1


Chemical compound and disease context of AKR1B1


Biological context of AKR1B1


Anatomical context of AKR1B1


Associations of AKR1B1 with chemical compounds


Physical interactions of AKR1B1


Enzymatic interactions of AKR1B1


Regulatory relationships of AKR1B1


Other interactions of AKR1B1

  • Many of the compounds which are substrates for AKR1A1 also serve as substrates for AKR1B1, though the latter enzyme was shown to display a specific activity significantly less than that of AKR1A1 for most of the aromatic and aliphatic aldehydes studied [18].
  • The members of all three superfamilies exhibit similar and low K(m) values for retinoids (0.12-1.1 microM), whilst they strongly differ in their kcat values, which range from 0.35 min(-1) for AKR1B1 to 302 min(-1) for ADH4 [22].
  • Human AR and HSI AR were very efficient in the reduction of all- trans -, 9- cis - and 13- cis -retinal ( k (cat)/ K (m)=1100-10300 mM(-1).min(-1)), constituting the first cytosolic NADP(H)-dependent retinal reductases described in humans [20].
  • The activities of aldose reductase and 3 alpha-hydroxysteroid dehydrogenase type 2 (106 and 35 nmol/mg/min, respectively) were higher than those of the other enzymes (0.2-4.0 nmol/mg/min) [31].
  • These observations suggest that AR is a critical regulator of TNF-alpha-induced apoptotic signaling in endothelial cells [26].

Analytical, diagnostic and therapeutic context of AKR1B1


  1. Decreased expression of cyclic adenosine monophosphate-regulated aldose reductase (AKR1B1) is associated with malignancy in human sporadic adrenocortical tumors. Lefrançois-Martinez, A.M., Bertherat, J., Val, P., Tournaire, C., Gallo-Payet, N., Hyndman, D., Veyssière, G., Bertagna, X., Jean, C., Martinez, A. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  2. Altered aldose reductase gene regulation in cultured human retinal pigment epithelial cells. Henry, D.N., Del Monte, M., Greene, D.A., Killen, P.D. J. Clin. Invest. (1993) [Pubmed]
  3. All in the family: aldose reductase and closely related aldo-keto reductases. Petrash, J.M. Cell. Mol. Life Sci. (2004) [Pubmed]
  4. The role of cytoplasmic intermediates in IL 2-induced T cell growth. Gutowski, J.K., Mukherji, B., Cohen, S. J. Immunol. (1984) [Pubmed]
  5. Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist. Sallinen, J., Link, R.E., Haapalinna, A., Viitamaa, T., Kulatunga, M., Sjöholm, B., Macdonald, E., Pelto-Huikko, M., Leino, T., Barsh, G.S., Kobilka, B.K., Scheinin, M. Mol. Pharmacol. (1997) [Pubmed]
  6. Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. Saruwatari, J., Matsunaga, M., Ikeda, K., Nakao, M., Oniki, K., Seo, T., Mihara, S., Marubayashi, T., Kamataki, T., Nakagawa, K. Eur. J. Clin. Pharmacol. (2006) [Pubmed]
  7. Erythrocyte aldose reductase correlates with erectile dysfunction in diabetic patients. Naya, Y., Soh, J., Ochiai, A., Mizutani, Y., Kawauchi, A., Fujito, A., Ushijima, S., Ono, T., Iwamoto, N., Aoki, T., Imada, N., Nakamura, N., Yabe-Nishimura, C., Miki, T. Int. J. Impot. Res. (2002) [Pubmed]
  8. Renal medullary organic osmolytes. Garcia-Perez, A., Burg, M.B. Physiol. Rev. (1991) [Pubmed]
  9. Nerve glucose, fructose, sorbitol, myo-inositol, and fiber degeneration and regeneration in diabetic neuropathy. Dyck, P.J., Zimmerman, B.R., Vilen, T.H., Minnerath, S.R., Karnes, J.L., Yao, J.K., Poduslo, J.F. N. Engl. J. Med. (1988) [Pubmed]
  10. Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. Sima, A.A., Bril, V., Nathaniel, V., McEwen, T.A., Brown, M.B., Lattimer, S.A., Greene, D.A. N. Engl. J. Med. (1988) [Pubmed]
  11. Highly selective aldose reductase inhibitors. 3. Structural diversity of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids. Kotani, T., Nagaki, Y., Ishii, A., Konishi, Y., Yago, H., Suehiro, S., Okukado, N., Okamoto, K. J. Med. Chem. (1997) [Pubmed]
  12. Stereospecific interaction of a novel spirosuccinimide type aldose reductase inhibitor, AS-3201, with aldose reductase. Kurono, M., Fujiwara, I., Yoshida, K. Biochemistry (2001) [Pubmed]
  13. A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes. Carper, D.A., Wistow, G., Nishimura, C., Graham, C., Watanabe, K., Fujii, Y., Hayashi, H., Hayaishi, O. Exp. Eye Res. (1989) [Pubmed]
  14. Metabolism of the 2-oxoaldehyde methylglyoxal by aldose reductase and by glyoxalase-I: roles for glutathione in both enzymes and implications for diabetic complications. Vander Jagt, D.L., Hassebrook, R.K., Hunsaker, L.A., Brown, W.M., Royer, R.E. Chem. Biol. Interact. (2001) [Pubmed]
  15. Aldehyde and aldose reductases from human placenta. Heterogeneous expression of multiple enzyme forms. Vander Jagt, D.L., Hunsaker, L.A., Robinson, B., Stangebye, L.A., Deck, L.M. J. Biol. Chem. (1990) [Pubmed]
  16. Kinetic characteristics of ZENECA ZD5522, a potent inhibitor of human and bovine lens aldose reductase. Cook, P.N., Ward, W.H., Petrash, J.M., Mirrlees, D.J., Sennitt, C.M., Carey, F., Preston, J., Brittain, D.R., Tuffin, D.P., Howe, R. Biochem. Pharmacol. (1995) [Pubmed]
  17. Purification and properties of aldose reductase and aldehyde reductase II from human erythrocyte. Das, B., Srivastava, S.K. Arch. Biochem. Biophys. (1985) [Pubmed]
  18. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. O'connor, T., Ireland, L.S., Harrison, D.J., Hayes, J.D. Biochem. J. (1999) [Pubmed]
  19. Identification of candidate predictive markers of anticancer drug sensitivity using a panel of human cancer cell lines. Dan, S., Shirakawa, M., Mukai, Y., Yoshida, Y., Yamazaki, K., Kawaguchi, T., Matsuura, M., Nakamura, Y., Yamori, T. Cancer Sci. (2003) [Pubmed]
  20. Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism. Crosas, B., Hyndman, D.J., Gallego, O., Martras, S., Parés, X., Flynn, T.G., Farrés, J. Biochem. J. (2003) [Pubmed]
  21. The crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding. Ye, Q., Hyndman, D., Green, N.C., Li, L., Jia, Z., Flynn, T.G. Chem. Biol. Interact. (2001) [Pubmed]
  22. Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids. Gallego, O., Belyaeva, O.V., Porté, S., Ruiz, F.X., Stetsenko, A.V., Shabrova, E.V., Kostereva, N.V., Farrés, J., Parés, X., Kedishvili, N.Y. Biochem. J. (2006) [Pubmed]
  23. Probing the active site of human aldose reductase. Site-directed mutagenesis of Asp-43, Tyr-48, Lys-77, and His-110. Tarle, I., Borhani, D.W., Wilson, D.K., Quiocho, F.A., Petrash, J.M. J. Biol. Chem. (1993) [Pubmed]
  24. Inactivation of carbonyl reductase from human brain by phenylglyoxal and 2,3-butanedione: a comparison with aldehyde reductase and aldose reductase. Bohren, K.M., von Wartburg, J.P., Wermuth, B. Biochim. Biophys. Acta (1987) [Pubmed]
  25. Characterization of the osmotic response element of the human aldose reductase gene promoter. Ruepp, B., Bohren, K.M., Gabbay, K.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  26. Aldose reductase regulates TNF-alpha-induced cell signaling and apoptosis in vascular endothelial cells. Ramana, K.V., Bhatnagar, A., Srivastava, S.K. FEBS Lett. (2004) [Pubmed]
  27. Decreased degradation of collagen and fibronectin following exposure of proximal cells to glucose. Phillips, A.O., Morrisey, K., Steadman, R., Williams, J.D. Exp. Nephrol. (1999) [Pubmed]
  28. Elevated activity of transcription factor nuclear factor of activated T-cells 5 (NFAT5) and diabetic nephropathy. Yang, B., Hodgkinson, A.D., Oates, P.J., Kwon, H.M., Millward, B.A., Demaine, A.G. Diabetes (2006) [Pubmed]
  29. Aldose reductase regulates TGF-beta1-induced production of fibronectin and type IV collagen in cultured rat mesangial cells. Jiang, T., Che, Q., Lin, Y., Li, H., Zhang, N. Nephrology (Carlton, Vic.) (2006) [Pubmed]
  30. The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy. Hodgkinson, A.D., Bartlett, T., Oates, P.J., Millward, B.A., Demaine, A.G. Diabetes (2003) [Pubmed]
  31. Tetrahydrobiopterin is synthesized from 6-pyruvoyl-tetrahydropterin by the human aldo-keto reductase AKR1 family members. Iino, T., Tabata, M., Takikawa, S., Sawada, H., Shintaku, H., Ishikura, S., Hara, A. Arch. Biochem. Biophys. (2003) [Pubmed]
  32. A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography. Oka, M., Matsumoto, Y., Sugiyama, S., Tsuruta, N., Matsushima, M. J. Med. Chem. (2000) [Pubmed]
  33. Purification and characterization of human testis aldose and aldehyde reductase. Tanimoto, T., Ohta, M., Tanaka, A., Ikemoto, I., Machida, T. Int. J. Biochem. (1991) [Pubmed]
  34. Inhibitory effects of fidarestat on aldose reductase and aldehyde reductase activity evaluated by a new method using HPLC with post-column spectrophotometric detection. Mizuno, K., Suzuki, T., Tanaka, T., Taniko, K., Suzuki, T. Biol. Pharm. Bull. (2000) [Pubmed]
  35. Aldose reductase in human retinal pigment epithelial cells. Sato, S., Lin, L.R., Reddy, V.N., Kador, P.F. Exp. Eye Res. (1993) [Pubmed]
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