DINITROBENZENES STIMULATE ELECTRON FLUX WITHIN NEURONAL NITRIC OXIDE SYNTHASE IN THE ABSENCE OF CALMODULIN

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

David A. Tulis (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Efficient electron transfer and conversion of L-arginine to L-citrulline and nitric oxide NO●) by neuronal nitric oxide synthase (nNOS) requires calmodulin (CaM) binding. The resent study focused on electron transfer ability of resting state CaM-free nNOS in resence of dinitrobenzene isomers (DNBs). NADPH oxidation (NADPHox) and acetylated cytochrome-c reduction (AcCyt-cred) catalyzed by nNOS and the CaM binding sequencedeficient nNOS reductase construct (nNOS-FP) were estimates of total electron flux and O2● production respectively. All the DNBs (o- m- p-) independently stimulated rates of NADPHox by CaM-free nNOS and by nNOS-FP in isomer- and concentration-dependent manner. Blocking nNOS heme by imidazole or L-arginine did not affect CaM-free nNOS catalyzed NADPHox stimulated by DNBs. This stimulated electron flux by DNBs did not support NO● formation by CaM-free nNOS. The DNBs like FeCN extract electrons from both FMN and FAD of the nNOS reductase domain. All three DNBs greatly stimulated nNOS and nNOS-FP catalyzed AcCyt-cred that was significantly inhibited by SOD demonstrating O2● formation. Thus in presence of DNBs resting-state CaM-deficient nNOS efficiently transfers electrons generating O2 — inferring that additional metabolic roles for nNOS exist that are not yet explored.

Additional Information

Publication

Other

International Journal of Biomedical Research 2 No. 9 (2011): 499-507.

Language: English

Date: 2013

Keywords

nNOS, superoxide, NADPH, redox

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