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Kinetic Alteration of Human Aldose Reductase by Mutagenesis of Cysteine Residues

  • J. Mark Petrash
  • Theresa Harter
  • Ivan Tarle
  • David Borhani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 328)

Abstract

Aldose reductase (ALR21: alditol:NADPH oxidoreductase: E.C. 1.1.1.21) catalyzes the NADPH-linked reduction of aldoses to their corresponding alcohols or polyols, the first step of the polyol pathway. Enhanced flux of glucose through the polyol pathway and consequent biochemical imbalances are thought to be crucial to the onset and progression of many complications of diabetes mellitus including cataract, retinopathy, neuropathy and nephropathy (Kinoshita and Nishimura, 1988). In light of its rate-limiting position in the polyol pathway as well as its apparent metabolic dispensability (Yancey et al., 1990), strategies to control or prevent the onset of diabetic complications through inhibition of aldose reductase are being aggressively pursued. While a structurally-diverse array of aldose reductase inhibitors (ARI) have yielded impressive results in animal studies, their effectiveness in arresting or preventing diabetic neuropathy (Boulton et al., 1990) and retinopathy (Sorbinil Retinopathy Trial Research Group, 1990) in human trials has been less encouraging (Frank, 1990).

Keywords

Cysteine Residue Aldose Reductase Polyol Pathway Aldose Reductase Inhibitor Aldose Reductase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • J. Mark Petrash
    • 1
  • Theresa Harter
    • 1
  • Ivan Tarle
    • 1
  • David Borhani
    • 2
  1. 1.Departments of Ophthalmology and Visual Sciences and of GeneticsWashington University School of MedicineSt. LouisUSA
  2. 2.BioCryst Pharmaceuticals, Inc.BirminghamUSA

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