C60-Fullerene Monomalonate Adducts Selectively Inactivate Neuronal Nitric Oxide Synthase by Uncoupling the Formation of Reactive Oxygen Intermediates from Nitric Oxide Production
- 9 December 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 40 (1) , 37-45
- https://doi.org/10.1021/bi0019444
Abstract
C60-Fullerene monomalonate adducts inactivate selectively the neuronal nitric oxide synthase isoform in a manner completely preventable by the concurrent presence of superoxide dismutase and catalase. This inactivation is time-, fullerene concentration-, and turnover-dependent and is not reversible by dilution. The di(carboxypropan-3-ol)methano-[60]-fullerene (diol adduct) has no effect on NADPH consumption by nNOS as measured in the absence of arginine substrate, but dramatically increases NADPH consumption in the presence of arginine. This fullerene-enhanced NADPH consumption is linked to oxygen as electron acceptor and is accompanied by the increased production of hydrogen peroxide. These effects of fullerene monomalonate adducts are unique to the nNOS isoform and are not observed using either the iNOS or the eNOS isoform. The inhibitory effects of fullerene monomalonate adducts are unaltered and insurmountable by increased concentrations of arginine, tetrahydrobiopterin, or calmodulin. These observations indicate that fullerene monomalonate adducts uncouple in the presence of arginine the formation of reactive oxygen intermediates from NO production by nNOS. These reactive oxygen intermediates dissociate from the enzyme and, acting from solution, inactivate NOS NO forming activity.Keywords
This publication has 16 references indexed in Scilit:
- Inhibition of Nitric Oxide Synthase Isoforms by Tris-Malonyl-C60-Fullerene AdductsArchives of Biochemistry and Biophysics, 2000
- Synthesis and Characterization of Water-Soluble Amino Fullerene DerivativesOrganic Letters, 2000
- NITRIC OXIDE AND MACROPHAGE FUNCTIONAnnual Review of Immunology, 1997
- Differentiation of Isomers Resulting from Bisaddition to C60 Using 3He NMR SpectrometryJournal of the American Chemical Society, 1996
- [2 + 2] Photocycloaddition of Cyclic Enones to C60Journal of the American Chemical Society, 1996
- Nitric Oxide Synthases: Properties and Catalytic MechanismAnnual Review of Physiology, 1995
- Photoinduced biochemical activity of fullerene carboxylic acidJournal of the American Chemical Society, 1993
- Suppression of arthritis by an inhibitor of nitric oxide synthase.The Journal of Experimental Medicine, 1993
- Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verificationJournal of the American Chemical Society, 1993
- Nitric oxide, a novel neuronal messengerNeuron, 1992