The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

LOC548613  -  aldo-keto reductase family 1, member B1...

Bos taurus

 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of ALR2

 

Psychiatry related information on ALR2

 

High impact information on ALR2

  • The effectiveness of cysteine and cysteinylglycine to act as protein thiolating agents was investigated using bovine lens aldose reductase (ALR2) as the protein target [4].
  • Both Cys-ALR2 and CysGly-ALR2 essentially retain the ability to reduce glyceraldehyde but lose the susceptibility to inhibition by Sorbinil and other ALR2 inhibitors [4].
  • Cysteine- and CysGly-modified ALR2 forms (Cys-ALR2 and CysGly-ALR2, respectively) are characterized by the presence of a mixed disulfide bond involving Cys298, as demonstrated by a combined electrospray mass spectrometry and Edman degradation approach [4].
  • Disulfides of both thiol compounds appear to be very effective as ALR2 thiolating agents [4].
  • Cys-ALR2 and CysGly-ALR2 are easily reduced back to the native enzyme form by dithiothreitol and GSH treatment; on the contrary, Cys and 2-mercaptoethanol appear to act as protein trans-thiolating agents, rather than reducing agents [4].
 

Biological context of ALR2

  • The inhibitory capability of the most effective compounds (IC50 values ranging from 6.44 to 12.6 microM) appears to be associated with a rather significant specificity for ALR2 [5].
  • Preparations of bovine lens ALR2 exhibit biphasic kinetics with respect to glucose and various inhibitors including ICI 215918 [6].
  • Besides being a general feature of protein reactivity in oxidative conditions, the glutathione-mediated ALR2 modification might be part of a cell strategy to preserve reducing power in conditions of oxidative stress [7].
  • Specific interactions of the bound glutathionyl moiety (GS) with the ALR2 active site, were predicted by a low perturbative molecular modelling approach [8].
 

Anatomical context of ALR2

  • A notable exception was the absence of detectable ALR2 in human erythrocytes [9].
  • The results presented here for the ALR2 level in human tissues (adrenal greater than muscle greater than lens approximately brain approximately testes greater than kidney approximately placenta) are in agreement with literature values for those tissues from which the enzyme has previously been purified [9].
 

Associations of ALR2 with chemical compounds

  • Additional evidence for strong interaction of ALR2 with both NADP+ and NADPH is reported [10].
  • GSH significantly interferes with the Cu-dependent inactivation of ALR2 and induces, through its oxidation to GSSG, the generation of an enzyme form linked to a glutathionyl residue by a disulfide bond [11].
  • Bovine kidney aldose reductase (ALR2) displays substrate inhibition by aldehyde substrates that is uncompetitive versus NADPH when allowance is made for nonenzymic reaction of the aldehyde with the adenine moiety of NADPH [3].
  • While metal chelators such as EDTA or o-phenantroline prevent but do not reverse the ALR2 inactivation, DTT allows the enzyme activity to be rescued by inducing the recovery of the native enzyme form [11].
  • Bovine lens aldose reductase (ALR2) is inactivated by copper ion [Cu(II)] through an oxygen-independent oxidative modification process [11].
 

Analytical, diagnostic and therapeutic context of ALR2

References

  1. Ponalrestat: a potent and specific inhibitor of aldose reductase. Ward, W.H., Sennitt, C.M., Ross, H., Dingle, A., Timms, D., Mirrlees, D.J., Tuffin, D.P. Biochem. Pharmacol. (1990) [Pubmed]
  2. Inhibition of hexonate dehydrogenase and aldose reductase from bovine retina by sorbinil, statil, M79175 and valproate. Poulsom, R. Biochem. Pharmacol. (1986) [Pubmed]
  3. Mechanistic basis for nonlinear kinetics of aldehyde reduction catalyzed by aldose reductase. Grimshaw, C.E., Shahbaz, M., Putney, C.G. Biochemistry (1990) [Pubmed]
  4. Thiol/disulfide interconversion in bovine lens aldose reductase induced by intermediates of glutathione turnover. Vilardo, P.G., Scaloni, A., Amodeo, P., Barsotti, C., Cecconi, I., Cappiello, M., Lopez Mendez, B., Rullo, R., Dal Monte, M., Del Corso, A., Mura, U. Biochemistry (2001) [Pubmed]
  5. Synthesis, activity, and molecular modeling of a new series of tricyclic pyridazinones as selective aldose reductase inhibitors. Costantino, L., Rastelli, G., Vescovini, K., Cignarella, G., Vianello, P., Corso, A.D., Cappiello, M., Mura, U., Barlocco, D. J. Med. Chem. (1996) [Pubmed]
  6. (2,6-Dimethylphenylsulphonyl)nitromethane: a new structural type of aldose reductase inhibitor which follows biphasic kinetics and uses an allosteric binding site. Ward, W.H., Cook, P.N., Mirrlees, D.J., Brittain, D.R., Preston, J., Carey, F., Tuffin, D.P., Howe, R. Biochem. Pharmacol. (1991) [Pubmed]
  7. Glutathione dependent modification of bovine lens aldose reductase. Cappiello, M., Voltarelli, M., Giannessi, M., Cecconi, I., Camici, G., Manao, G., Del Corso, A., Mura, U. Exp. Eye Res. (1994) [Pubmed]
  8. Modulation of aldose reductase activity through S-thiolation by physiological thiols. Cappiello, M., Amodeo, P., Mendez, B.L., Scaloni, A., Vilardo, P.G., Cecconi, I., Dal Monte, M., Banditelli, S., Talamo, F., Micheli, V., Giblin, F.J., Corso, A.D., Mura, U. Chem. Biol. Interact. (2001) [Pubmed]
  9. Immunoquantitation of aldose reductase in human tissues. Grimshaw, C.E., Mathur, E.J. Anal. Biochem. (1989) [Pubmed]
  10. Spectroscopic and kinetic characterization of nonenzymic and aldose reductase mediated covalent NADP-glycolaldehyde adduct formation. Grimshaw, C.E., Shahbaz, M., Putney, C.G. Biochemistry (1990) [Pubmed]
  11. Oxidative modification of aldose reductase induced by copper ion. Factors and conditions affecting the process. Cecconi, I., Moroni, M., Vilardo, P.G., Dal Monte, M., Borella, P., Rastelli, G., Costantino, L., Garland, D., Carper, D., Petrash, J.M., Del Corso, A., Mura, U. Biochemistry (1998) [Pubmed]
  12. Oxidative modification of aldose reductase induced by copper ion. Definition of the metal-protein interaction mechanism. Cecconi, I., Scaloni, A., Rastelli, G., Moroni, M., Vilardo, P.G., Costantino, L., Cappiello, M., Garland, D., Carper, D., Petrash, J.M., Del Corso, A., Mura, U. J. Biol. Chem. (2002) [Pubmed]
  13. Aldose reductase does catalyse the reduction of glyceraldehyde through a stoichiometric oxidation of NADPH. Del Corso, A., Costantino, L., Rastelli, G., Buono, F., Mura, U. Exp. Eye Res. (2000) [Pubmed]
 
WikiGenes - Universities