What is Nitric Oxide Synthase?

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  • Written By: M.J. Casey
  • Edited By: Daniel Lindley
  • Last Modified Date: 05 September 2019
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Nitric acid (NO) is a small molecule with a double covalent bond between nitrogen and oxygen atoms. It is produced in the human body by a two-step synthesis from the amino acid arginine, catalyzed by the enzyme nitric oxide synthase (NOS). NOS is present in three forms in different tissues. The highly reactive NO is produced as a stress response and is both a cytotoxin and a cytoprotective agent.

A free radical, nitric oxide has toxic effects on host and bacterial cells. Its production in epithelial cells is controlled by epithelial nitric oxide synthase (eNOS). Nitric oxide synthase is bound in the cell’s membrane on the cytoplasm side or in the membranes of various organelles. NO in epithelial cells is instrumental in controlling vascular contraction and dilation. Anchoring eNOS in the cell membrane helps the cell restrict the activity of NO to small sites.

Inducible nitric oxide synthase (iNOS) is employed by the body to stall the growth of cells in gastric epithelial, breast, and brain tumors. NO made by the action of iNOS disables energy metabolism by reacting with the cell’s deoxyribonucleic acid (DNA) and ultimately kills the cell. Good tissue may be injured in the fight to kill tumor cells. Likewise, NO synthesized with eNOS fights the invasion of bacterial cells while indiscriminately killing surrounding somatic cells. Either type of host cell death can lead to toxic shock, a serious complication for patients with compromised immune systems.


In and around nerve cells, NO acts as a short-term signal transmitter, diffusing easily across membranes. Neuronal nitric oxide synthase (nNOS) is continuously recycled to produce NO, as the NO is stable for mere seconds before being neutralized by water molecules. The expression of the enzyme is regulated by calcium ion concentration. NO is believed to be involved in the conversion of short-term to long-term memory through a process called long-term potentiation (LTP).

Inhibitors of nitric oxide synthase are neuroprotective, as they reduce the availability of the free radical NO. Compounds in this class include hydrophilic vitamin C and hydrophobic Vitamin E. These and other molecules have been investigated with the hope of slowing neurodegenerative conditions such as Parkinson’s disease. As of 2010, direct links have not been demonstrated. One fear is that by decreasing the activity of nitric oxide synthase, neurons may be protected but memories may be lost.


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