![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
NS Kolb, LA Hunsaker and DL Vander Jagt
Department of Biochemistry, University of New Mexico School of Medicine, Albuquerque 87131.
Acrolein, a highly cytotoxic aldehyde, is a metabolic by-product of the antineoplastic agent cyclophosphamide and is responsible for the development of hemorrhagic cystitis, a serious side effect of cyclophosphamide therapy. Aldose reductase (EC 1.1.1.21), a member of the aldo-keto reductase superfamily, catalyzes the NADPH-dependent reduction of acrolein to allyl alcohol (Km = 80 microM, kcat = 87 min- 1). Aldose reductase is expressed at different levels in individuals. This suggests that individual differences in the reductive metabolism of acrolein may be a determinant of acrolein toxicity. In addition to being a substrate, acrolein also produces a time-dependent 7-20-fold increase in the activity of aldose reductase toward a variety of substrates. This involves initial binding of acrolein to a second site (Ks = 58 microM). Acrolein activation of aldose reductase results not only in higher kcat values for all substrates but also in higher Km values and decreased catalytic efficiencies. Acrolein activation of aldose reductase reduces its affinity for aldose reductase inhibitors.
This article has been cited by other articles:
|
|
 |
|
  R. K. Thimmulappa, K. H. Mai, S. Srisuma, T. W. Kensler, M. Yamamoto, and S. Biswal Identification of Nrf2-regulated Genes Induced by the Chemopreventive Agent Sulforaphane by Oligonucleotide Microarray Cancer Res., September 15, 2002; 62(18): 5196 - 5203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kobayashi, T. Kaneko, Y. Iuchi, S. Matsuki, M. Takahashi, I. Sasagawa, T. Nakada, and J. Fujii Localization and Physiological Implication of Aldose Reductase and Sorbitol Dehydrogenase in Reproductive Tracts and Spermatozoa of Male Rats J Androl, September 1, 2002; 23(5): 674 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kaneko, Y. Iuchi, S. Kawachiya, T. Fujii, H. Saito, H. Kurachi, and J. Fujii Alteration of Glutathione Reductase Expression in the Female Reproductive Organs During the Estrous Cycle Biol Reprod, November 1, 2001; 65(5): 1410 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. G. Seo, T. Nishinaka, and C. Yabe-Nishimura Nitric Oxide Up-Regulates Aldose Reductase Expression in Rat Vascular Smooth Muscle Cells: A Potential Role for Aldose Reductase in Vascular Remodeling Mol. Pharmacol., April 1, 2000; 57(4): 709 - 717. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Colrat, A. Latché, M. Guis, J.-C. Pech, M. Bouzayen, J. Fallot, and J.-P. Roustan Purification and Characterization of a NADPH-Dependent Aldehyde Reductase from Mung Bean That Detoxifies Eutypine, a Toxin from Eutypa lata1 Plant Physiology, February 1, 1999; 119(2): 621 - 626. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Yabe-Nishimura Aldose Reductase in Glucose Toxicity: A Potential Target for the Prevention of Diabetic Complications Pharmacol. Rev., March 1, 1998; 50(1): 21 - 34. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
