Human Nitric Oxide Synthase-Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases

Int J Mol Sci. 2020 Dec 23;22(1):56. doi: 10.3390/ijms22010056.

Abstract

In various diseases, there is an increased production of the free radicals needed to carry out certain physiological processes but their excessive amounts can cause oxidative stress and cell damage. Enzymes play a major role in the transformations associated with free radicals. One of them is nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO). This enzyme exists in three forms (NOS1, NOS2, NOS3), each encoded by a different gene. The following work presents the most important information on the NOS isoforms and their role in the human body, including NO synthesis in various tissues and cells, intercellular signaling and activities supporting the immune system and regulating blood vessel functions. The role of NOS in pathological conditions such as obesity, diabetes and heart disease is considered. Attention is also paid to the influence of the polymorphisms of these genes, encoding particular isoforms, on the development of these pathologies and the role of NOS inhibitors in the treatment of patients.

Keywords: heart diseases; nitric oxide synthase; obesity; oxidative stress; single nucleotide polymorphism; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / metabolism
  • Disease Susceptibility*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism
  • Insulin Resistance
  • Isoenzymes
  • Molecular Targeted Therapy
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / metabolism*
  • Obesity / etiology
  • Obesity / metabolism
  • Oxidative Stress
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Nitric Oxide
  • Nitric Oxide Synthase