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Biophys J, May 2001, p. 2110-2119, Vol. 80, No. 5
*Department of Chemical and Biochemical Engineering and Materials
Science,
The Center for Biomedical Engineering,
University of California, Irvine, Irvine, California 92697-2575 USA
Free nitric oxide (NO) activates soluble guanylate
cyclase (sGC), an enzyme, within both pulmonary and vascular smooth
muscle. sGC catalyzes the cyclization of guanosine 5'-triphosphate to guanosine 3',5'-cyclic monophosphate (cGMP). Binding rates of NO to the
ferrous heme(s) of sGC have been measured in vitro. However, a missing
link in our understanding of the control mechanism of sGC by NO is a
comprehensive in vivo kinetic analysis. Available literature data
suggests that NO dissociation from the heme center of sGC is
accelerated by its interaction with one or more cofactors in vivo. We
present a working model for sGC activation and NO consumption in vivo.
Our model predicts that NO influences the cGMP formation rate over a
concentration range of
5-100 nM (apparent Michaelis constant
23 nM), with Hill coefficients between 1.1 and 1.5. The apparent
reaction order for NO consumption by sGC is dependent on NO
concentration, and varies between 0 and 1.5. Finally, the activation of
sGC (half-life
1-2 s) is much more rapid than deactivation
(
50 s). We conclude that control of sGC in vivo is most likely
ultra-sensitive, and that activation in vivo occurs at lower NO
concentrations than previously reported.
Biophys J, May 2001, p. 2110-2119, Vol. 80, No. 5
© 2001 by the Biophysical Society 0006-3495/01/05/2110/10 $2.00
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