Inosine
Encyclopedia
Inosine is a nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...

 that is formed when hypoxanthine
Hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-Hydroxypurine. Hypoxanthine is a necessary additive in certain cell,...

 is attached to a ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

 ring (also known as a ribofuranose) via a β-N9-glycosidic bond
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....

.

Inosine is commonly found in tRNAs and is essential for proper translation of the genetic code in wobble base pair
Wobble base pair
In molecular biology, a wobble base pair is a non-Watson-Crick base pairing between two nucleotides in RNA molecules. The four main wobble base pairs are guanine-uracil, inosine-uracil, inosine-adenine, and inosine-cytosine . The thermodynamic stability of a wobble base pair is comparable to that...

s.

Knowledge of inosine metabolism has led to advances in immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...

 in recent decades. Inosine monophosphate is oxidised by the enzyme inosine monophosphate dehydrogenase, yielding xanthosine monophosphate
Xanthosine monophosphate
Xanthosine monophosphate is an intermediate in purine metabolism. It is a ribonucleoside monophosphate. It is formed from IMP via the action of IMP dehydrogenase, and it forms GMP via the action of GMP synthase.-Clinical significance:...

, a key precursor in purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 metabolism. Mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...

 is an anti-metabolite, anti-proliferative drug that acts as an inhibitor of inosine monophosphate dehydrogenase. It is used in the treatment of a variety of autoimmune diseases including Wegener's granulomatosis
Wegener's granulomatosis
Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...

 because the uptake of purine by actively dividing B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s can exceed 8 times that of normal body cells, and, therefore, this set of white cells (which cannot operate purine salvage pathways) is selectively targeted by the purine deficiency resulting from IMD inhibition.

Reactions

Adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...

 is converted to adenosine or inosine monophosphate (IMP), either of which, in turn, is converted into inosine (I), which pairs with Adenine (A), cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...

 (C), and uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...

 (U).

Purine nucleoside phosphorylase
Purine nucleoside phosphorylase
Purine nucleoside phosphorylase also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.- Function :Purine nucleoside phosphorylase is an enzyme involved in purine metabolism...

 intraconverts inosine and hypoxanthine
Hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-Hydroxypurine. Hypoxanthine is a necessary additive in certain cell,...

.

Inosine is also an intermediate in a chain of purine nucleotides reactions required for muscle movements.

Clinical significance

It was tried in the 1970s in Eastern countries for improving athletic performance. Nevertheless, the clinical trials for this purpose showed no improvement.
It has been shown that inosine has neuroprotective properties. It has been proposed for spinal cord injury; because it improves axonal rewiring, and for administration after stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, because observation has shown that axonal re-wiring is encouraged.

It is currently in phase II trials for multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 (MS). It produces uric acid after ingestion, which is a natural antioxidant and a peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...

 scavenger, which can suggest possible benefit in multiple sclerosis (peroxynitrite has been correlated with the axons degeneration http://www.fedem.org/revista/n17/neuhausing.htm).

It is also in phase II trials for Parkinson's disease. Earlier trials had suggested those with the highest serum urate levels had lower progression of Parkinson's symptoms. The trial uses inosine to raise urate levels in those with levels lower than the population mean (6 mg/dL).

Alseres Pharmaceuticals (named Boston Life Sciences when patent was granted) patented the treatment for stroke http://www.bostonlifesciences.com/news111.htm and is currently investigating the drug in the MS setting.

In the Anatomical Therapeutic Chemical Classification System
Anatomical Therapeutic Chemical Classification System
The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. It is controlled by the WHO Collaborating Centre for Drug Statistics Methodology , and was first published in 1976....

, it is classified as an antiviral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

.

Biotechnology

When designing primer
Primer (molecular biology)
A primer is a strand of nucleic acid that serves as a starting point for DNA synthesis. They are required for DNA replication because the enzymes that catalyze this process, DNA polymerases, can only add new nucleotides to an existing strand of DNA...

s for polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

, inosine is useful in that it will indiscriminately pair with adenine, thymine, or cytosine. This allows for design of primers that span a single-nucleotide polymorphism, without the polymorphism disrupting the primer's annealing efficiency.

Fitness

Despite lack of clinical evidence that it improves muscle development, inosine remains an ingredient in some fitness supplements.

Feeding Stimulant

Inosine has also been found to be an important feed stimulant by itself or in combination with certain amino acids in some species of farmed fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

. For example, inosine and inosine-5-monophosphate have been reported as specific feeding stimulants for turbot
Turbot
The turbot is a species of flatfish in the family Scophthalmidae. It is native to marine or brackish waters of the North Atlantic, Baltic Sea and the Mediterranean Sea.-Etymology:...

 fry, (Scophthalmus maximus) and yellowtail
Yellowtail
A yellowtail may be any of several different species of fish. Most commonly the Yellowtail amberjack Seriola lalandi is meant. In the context of sushi, yellowtail usually refers to the Japanese amberjack, Seriola quinqueradiata...

, (Seriola quinqueradiata). The main problem of using inosine and/or inosine-5-monophosphate as feeding attractants is their high cost. However, their use may be economically justified within larval feeds for marine fish larvae during the early weaning period, since the total quantity of feed consumed is relatively low.

Experimental

NOV-205 manufactured by Novelos Therapeutics is A new class of Antiviral medication that is approved for use in Russia under the tradename of "Molixan" and currently being tested in the USA under FDA clinical studies.

This medication follows the Glutathione pathway via GSSG and, therefore, acts as an immunomodulator, hepatoprotective, and anti-inflammatory.

Under oxidative stress (attack by virus at the cellular level), Oxidized Gluatathione (spent side) appears to modulate inosine, causing knock-out of "viral load."

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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