一酸化窒素 (NO) とNO合成酵素 (NOS)

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Nitric oxide (NO) is a gas radical generated from 1-arginine via enzymatic action of NO synthases (NOS) in the presence of calmodulin (CaM), NADPH, flavins (FMN, FAD), tetrahydrobiopterine, O2, and heme. NOS contains reductase domain at C-terminus and oxygenase domain at N-terminus. At least three isoforms of NOS exist. Neuronal and endothelial constitutive (c) NOS is a Ca2+/CaM dependent, while inducible (i) NOS is Ca2+ independent. NO generated by neuronal cNOS functions as a neurotransmitter in the central as well as in the peripheral neurons, while NO by endothelial cNOS regulates vascular tonus. iNOS is regulated at the transcriptional level by several cytokines and endotoxins. Overproduction of NO by iNOS in a variety of cells, such as macrophages, vascular endothelial and smooth muscle cells, cardiocytes etc., functions as a host defence mechanism by its bacteriocidal action. However, sustained and exaggerated production of NO contributes to the development of endotoxin shock and organ dysfunction associated with sepsis, and many localized inflammatory lesions. Regulation of three NOS isoforms genes, their knock-out gene mice, and their structure·function are reviewed.

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