Inosine is a

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar ( ribose or 2'-deoxyribose) whereas a nucleoti ...

that is formed when

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. H ...

is attached to a

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compou ...

ring (also known as a ribofuranose) via a β-N₉-

glycosidic bond A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal gr ...

. It was discovered in 1965 in analysis of RNA transferase. Inosine is commonly found in

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino a ...

s and is essential for proper translation of the genetic code in wobble base pairs. Knowledge of inosine metabolism has led to advances in

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

in recent decades. Inosine monophosphate is oxidised by the enzyme inosine monophosphate dehydrogenase, yielding

xanthosine monophosphate Xanthosine monophosphate also called Xanthylate is an intermediate in purine metabolism. It is a ribonucleoside monophosphate In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecul ...

, a key precursor in

purine Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purin ...

metabolism. Mycophenolate mofetil 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 In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

diseases including

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is a form of vasculitis ...

because the uptake of purine by actively dividing

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

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 inosine monophosphate dehydrogenase (IMD) inhibition.

Reactions

Adenine Adenine () (symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivativ ...

is converted to

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside buildin ...

or inosine monophosphate (IMP), either of which, in turn, is converted into inosine (I), which pairs with adenine (A),

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached ...

(C), and

uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced ...

(U). Purine nucleoside phosphorylase intraconverts inosine and

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

Clinical significance

In the 1970s, inosine was used by athletes in Eastern countries in an attempt to improve performance. Subsequent studies in humans suggest that inosine supplementation has no effect on athletic performance. Animal studies have suggested that inosine has neuroprotective properties. It has been proposed for spinal cord injury and for administration after stroke, because observation suggests that inosine induces axonal rewiring. After ingestion, inosine is metabolized into uric acid, which has been suggested to be a natural antioxidant and peroxynitrite scavenger with potential benefits to patients with multiple sclerosis (MS). Peroxynitrite has been correlated with axon degeneration In 2003, a study was initiated at the University of Pennsylvania MS Center to determine whether raising the levels of uric acid by the administration of inosine would slow the progression of MS. The study was completed in 2006 but the results were not reported to NIH. A subsequent publication hinted at potential benefits but the sample size (16 patients) was too small for a definitive conclusion. In addition, the side effect of the treatment was the development of kidney stones in four of 16 patients. With phase II trials for Parkinson's disease completed, inosine will continue to phase III trials. Earlier trials suggested that patients with the highest serum urate levels had slower 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 use of inosine to treat stroke and was investigating the drug in the MS setting. In the Anatomical Therapeutic Chemical Classification System, it is classified as an antiviral.

Binding

Inosine is a natural ligand for the benzodiazepine binding site on the GABA A receptor.

Biotechnology

When designing primers for

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...

, inosine is useful in that it can pair with any natural base. This allows for design of primers that span a

single-nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently lar ...

, without the polymorphism disrupting the primer's annealing efficiency. However, inosine pairs preferentially with cytosine (C) and its introduction to RNA, e.g. by the action of ADARs, thereby destabilizes double-stranded RNA by changing AU base-pairs to IU mismatches.

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 are aquatic, craniate, gill-bearing 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. Approximately 95% ...

. For example, inosine and inosine-5-monophosphate have been reported as specific feeding stimulants for turbot fry, (''Scophthalmus maximus'') and Japanese amberjack, (''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 small.

References

External links

PDR health study
{{Purinergics Nucleosides Purines Antiviral drugs Hydroxymethyl compounds Ophthalmology drugs