INOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated

NO is an important cellular signaling molecule, having a vital role in many biological processes. It is the intercellular signal that controls vascular tone (blood pressure), insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis (growth of new blood vessels) and in the development of nervous system. It is believed to function as a neurotransmitter and hence is likely to be important in learning.

NO-СИНТАЗА

Синтазы оксида азота, NO-синтазы (NO-synthase, NOS) - группа ферментов, катализирующих образование оксида азота и цитруллина из аргинина, кислорода и NADPH.

L-Arg + NADPH + H⁺ + O₂ → NOHLA + NADP⁺ + H₂O

NOHLA + ½ NADPH + ½ H⁺ + O₂ → L-citrulline + ½ NADP⁺ + NO + H₂O

L-arginine + 3/2 NADPH + H⁺ + 2 O₂ = citrulline + nitric oxide + 3/2 NADP⁺

NOS isoforms catalyze many other leak and side reactions such as superoxide production at the expense of NADPH, so this stoichiometry is not generally observed. The unusual stoichiometry reflects the three electrons supplied per NO by NADPH; NO is a free radical with an unpaired electron.

NOSs are unusual in that they require five cofactors. NOS binds flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, tetrahydrobiopterin (BH₄) and calmodulin.

Eukaryotic NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH --> FAD --> FMN--> heme --> O₂. Tetrahydrobiopterin provides an additional electron during the catalytic cycle which is replaced during turnover.

Классификация

Название	Гены	Локализация	Функции
Нейрональная NO-синтаза (nNOS или NOS1)	NOS1	нервная ткань	клеточная передача сигнала
Индуцируемая NO-синтаза (iNOS или NOS2)	NOS2A, NOS2B, NOS2C	иммунная система сердечно-сосудистая система	иммунная защита от патогенов
Эндотелиальная NO-синтаза (eNOS или NOS3 или cNOS)	NOS3	эндотелий	вазодилатация

NO produced by eNOS has been shown to be a vasodilator identical to the endothelium-derived relaxing factor. NO activates guanylate cyclase, which induces smooth muscle relaxation by:

• Increased intracellular cGMP, which inhibits calcium entry into the cell, and decreases intracellular calcium concentrations
• Activation of K⁺ channels, which leads to hyperpolarization and relaxation
• Stimulates a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation.

Дата добавления: 2014-01-14