Polymorphisms in endothelial nitric oxide synthase and carotid artery atherosclerosis
- 5 July 2006
- journal article
- review article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 60 (4), 341-344
- https://doi.org/10.1136/jcp.2006.040550
Abstract
NO is generated by the endothelial nitric oxide synthase (eNOS) gene (NOS3), which is highly polymorphic. Specifically, NO is constitutively generated from the conversion of l-arginine to l-citrulline by the enzymatic action of eNOS. Historically, eNOS was classified as a constitutively expressed enzyme regulated by calcium and calmodulin. In the past 5 years, it has become clear, however, that eNOS activity and NO release can be regulated by post-translational control mechanisms (fatty-acid modification and phosphorylation) and protein–protein interactions (with caveolin-1 and heat shock protein 90), which directly impinge on the duration and magnitude of NO release.4,5 eNOS is a membrane-associated NOS isoform that is modified by co-translational N-myristoylation at glycine 2 and post-translational cysteine palmitoylation at positions 15 and 26, and these fatty acids are important for its targeting in the Golgi region and plasmalemmal caveolae. The proper localisation of eNOS is necessary for its interactions with other regulatory proteins (scaffolds, chaperones, kinases) that fine-tune the cycles of eNOS activation and inactivation. The major negative regulatory protein for eNOS is caveolin-1. Caveolin-1 is the major coat protein of caveolae, and has several faces that may influence the biology of proteins that localise to cholesterol-rich plasmalemma caveolae. Caveolin-1 can serve …Keywords
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