Jump to main content
Jump to site search


Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

Author affiliations

Abstract

Numerous studies have shown that nitric oxide (NO) interacts with human cyclooxygenase (COX); however, conflicting results exist with respect to their interactions. Herein, recombinant human COX-1 and COX-2 were prepared and treated with NO donors individually under anaerobic and aerobic conditions. The S-nitrosylation detection and subsequent kinetic investigations into the arachidonic acid (AA) oxidation of COX enzymes indicate that NO S-nitrosylates both COX-1 and COX-2 in an oxygen-dependent manner, but enhances only the dioxygenase activity of COX-2. The solution viscosity, deuterium kinetic isotope effect (KIE), and oxygen-18 KIE experiments further demonstrate that NO activates COX-2 by altering the protein conformation to stimulate substrate association/product release and by accelerating the rate of hydrogen abstraction from AA by catalytic tyrosine radicals. These novel findings provide useful information for designing new drugs with less cardiotoxic effects that can block the interaction between NO and COX.

Graphical abstract: Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

Back to tab navigation

Supplementary files

Publication details

The article was received on 04 Dec 2017, accepted on 21 Dec 2017 and first published on 21 Dec 2017


Article type: Paper
DOI: 10.1039/C7OB02992F
Citation: Org. Biomol. Chem., 2018, Advance Article
  •   Request permissions

    Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

    J. Qiao, L. Ma, J. Roth, Y. Li and Y. Liu, Org. Biomol. Chem., 2018, Advance Article , DOI: 10.1039/C7OB02992F

Search articles by author

Spotlight

Advertisements