NO Syntheses and Functions

The study of Nitric Oxide (NO) started in the late 1980s when it was discovered to act as a signalling mediator in many of physiological processes, including regulation of blood flow, neurotransmission and immune response. This dicovery led to the 1998 Nobel prize awarded to R. Furchgott, L. Ignarro and F. Murad.

Nitric Oxide Syntheses:

Nitric oxide is a naturally occurring molecule found in a variety of cell types and organ systems. Nitric Oxide (NO) is produced by a group of enzymes called nitric oxide syntheses (NOS). These enzymes (present in body) convert the L-arginine into L-citrulline, producing NO in the process. Oxygen and NADPH are necessary co-factors.

There are three isoforms of NOS which have been named according to their activity. They are neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Our scientists commonly refer to these enzymes by number so that nNOS is known as NOS1, iNOS is NOS2, and eNOS is NOS3. Although there are three names, these isoforms can be found in a variety of tissues and cell types working toward the same biological functions. The general function of NO production from NOS is illustrated below in figure 1.

Nitric Oxide Functions:

There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. NO is an important regulator and mediator of numerous processes in cardiovascular systems (vascular smooth muscle relaxation, resulting in arterial vasodilation and increasing blood flow), the nervous, and immune.

Vasodilation

Nitric Oxide (NO) is of critical importance as a mediator of vasodilation in blood vessels induced by several factors. First, as soon as NO is synthesized by eNOS, it triggers phosphorylation of several proteins that cause smooth muscle relaxation (phosphorylation activates or deactivates many protein enzymes and plays a significant role in a wide range of cellular processes). Secondly, NO play a key role in renal control of extracellular fluid homeostasis and is essential for the regulation of blood flow and blood pressure. This role of NO helps maintenance of  the penis erection .

Neurotransmission

NO is also a neurotransmitter synthesized by nNOS,. It has been associated with neuronal activity and various functions of nerve cells. Unlike most other neurotransmitters that only transmit information from apresynaptic to a postsynaptic neuron, the fat-soluble nitric oxide molecule can act on several nearby neurons and quickly diffuse in cells. NO is involved not only in the process of learning and memorizing, but also in various parts of the gastrointestinal tract, causing relaxation of the gastrointestinal smooth muscle. In the stomach it increases the capacity of the fundus to store food/fluids.

Immune system

Macrophages, certain cells of the immune system, produce nitric oxide in order to kill invading bacteria. In this case, the nitric oxide synthase is is synthesized by iNOS.

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