Active site modification of aldose reductase by nitric oxide donors

Animesh Chandra, Sanjay Srivastava, J. Mark Petrash, Aruni Bhatnagar, Satish Srivastava

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Nitric oxide (NO) donors sodium nitrosoprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonemine (SIN-1) caused a time- and concentration-dependent loss of catalytic activity of recombinant human placental aldose reductase. Modification of the enzyme was prevented by NADPH and NADP and reversed partially by dithiothreitol (DTT) and sodium borohydride. The protection by NADPH was lost in the presence of both substrates (NADPH and glyceraldehyde), indicating that the enzyme becomes sensitive to inhibition by SNP during catalysis. Site-directed mutant form of the enzyme, in which active site cys-298 was substituted with serine (C298S) was not inactivated by NO donors, whereas, ARC80S and ARC303 were as sensitive as the wild type enzyme, indicating that inactivation of aldose reductase is due to modification of the active site at cys298. These results suggest that NO may be an endogenous regulator of aldose reductase, and consequently the polyol pathway of glucose metabolism; which has been implicated in the pathogenesis of secondary diabetic complications.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volume1341
Issue number2
DOIs
StatePublished - Sep 5 1997

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Aldehyde Reductase
Nitric Oxide Donors
NADP
Catalytic Domain
Enzymes
Sodium
S-Nitroso-N-Acetylpenicillamine
Glyceraldehyde
Dithiothreitol
Diabetes Complications
Catalysis
Metabolism
Human Activities
Serine
Catalyst activity
Nitric Oxide
Glucose
Substrates

Keywords

  • Active site
  • Aldose reductase
  • Nitric oxide
  • Nitric oxide donor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Structural Biology
  • Biophysics

Cite this

Active site modification of aldose reductase by nitric oxide donors. / Chandra, Animesh; Srivastava, Sanjay; Petrash, J. Mark; Bhatnagar, Aruni; Srivastava, Satish.

In: Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology, Vol. 1341, No. 2, 05.09.1997, p. 217-222.

Research output: Contribution to journalArticle

Chandra, Animesh ; Srivastava, Sanjay ; Petrash, J. Mark ; Bhatnagar, Aruni ; Srivastava, Satish. / Active site modification of aldose reductase by nitric oxide donors. In: Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology. 1997 ; Vol. 1341, No. 2. pp. 217-222.
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