The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1914 by Japanese researchers Yatarō Koga (古賀彌太郎) and Ryō Ōtake (大嶽了) and further codified by Mitsunori Wada of Tokyo Imperial University in 1930. It has the formula H2NC(O)NH(CH2)3CH(NH2)CO2H. It is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase.
Agmatine, also known as 4-aminobutyl-guanidine, was discovered in 1910 by Albrecht Kossel. It is a chemical substance which is naturally created from the amino acid arginine. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, ion channels, nitric oxide (NO) synthesis, and polyamine metabolism and this provides bases for further research into potential applications.
Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.
Indazole, also called isoindazole, is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and pyrazole.
Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.
Spermidine is a polyamine compound found in ribosomes and living tissues and having various metabolic functions within organisms.
Argininosuccinate synthase or synthetase is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate. In humans, argininosuccinate synthase is encoded by the ASS gene located on chromosome 9.
Nicorandil is a vasodilator drug used to treat angina.
Louis Joseph Ignarro is an American pharmacologist. For demonstrating the signaling properties of nitric oxide, he was co-recipient of the 1998 Nobel Prize in Physiology or Medicine with Robert F. Furchgott and Ferid Murad.
N-Acetylserotonin (NAS), also known as normelatonin, is a naturally occurring chemical intermediate in the endogenous production of melatonin from serotonin. It also has biological activity in its own right, including acting as a melatonin receptor agonist, an agonist of the TrkB, and having antioxidant effects.
Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.
Nitric oxide synthase 1 (neuronal), also known as NOS1, is an enzyme that in humans is encoded by the NOS1 gene.
In the field of enzymology, a dimethylargininase, also known as a dimethylarginine dimethylaminohydrolase (DDAH), is an enzyme that catalyzes the chemical reaction:
Dynein light chain 1, cytoplasmic is a protein that in humans is encoded by the DYNLL1 gene.
COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of nonsteroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.
Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.
Biological functions of nitric oxide are roles that nitric oxide plays within biology.
Nitroarginine, or Nω-nitro-l-arginine, also known as L-NOARG, is a nitro derivative of the amino acid arginine. It is an inhibitor of nitric oxide synthase and hence a vasoconstrictor. As such, it finds widespread use as a biochemical tool in the study of nitric oxide and its biological effects.
Proadifen (SKF-525A) is a non-selective inhibitor of cytochrome P450 enzymes, preventing some types of drug metabolism. It is also an inhibitor of neuronal nitric oxide synthase (NOS), CYP-dependent arachidonate metabolism, transmembrane calcium influx, and platelet thromboxane synthesis. Further documented effects include the blockade of ATP-sensitive inward rectifier potassium channel 8 (KIR6.1), and stimulation of endothelial cell prostacyclin production.
David S. Bredt is an American molecular neuroscientist.
