Inosine is a nucleoside of RNA belonging to the purine base group and is synthesized from the nucleic base adenine via the intermediate hypoxanthine. The rarely occurring inosine with attached D-ribose as a sugar molecule has special functions. As the only nucleic base, inosine has the possibility, in the phosphorylated form as a nucleotide, to form pairings as complementary partners (anticodons) not only with one, but optionally with the three nucleic bases cytosine, adenine, guanine and thymine.
What is inosine?
Inosine is a nucleoside found exclusively in RNA that is synthesized from adenosine via hypoxanthine as an intermediate in the metabolism of nucleic bases. The modified bicyclic five- and six-membered ring of purine serves as the backbone. The attached ribose sugar molecule consists of the pentose beta-D-ribofuranose. The chemical molecular formula C10H12N4O5 indicates that inosine consists exclusively of carbon, hydrogen, nitrogen and oxygen, substances that are ubiquitously available. Rare trace elements or minerals are not needed for the synthesis of inosine. Normally, nucleic bases each form a bond with a specific other nucleic base via hydrogen bonds as complementary partners. Inosine, which occurs rarely, is the only nucleoside in RNA that can optionally form pairings with the nucleic bases cytosine, adenine, guanine, and thymine as complementary partners. The possible pairings are associated with increased energetic expenditure for the body, especially if only guanine or thymine are available as complementary bases. Inosine, like the other nucleic bases, can be recycled or else completely degraded to uric acid in the liver via purine metabolism.
Function, effects, and roles
Inosine is produced as part of the process known as RNA editing, in which the original nucleoside or nucleotide sequence of DNA in the copied form of messenger RNA (mRNA) no longer matches. The essential biochemical process is that adenosine, as the initial substance, is converted to inosine by the enzyme adenosine deaminase (ADA) through deamination and water splitting. The analogous process also occurs in the conversion of deoxyadenosine to deoxyinosine. The enzyme can be detected in almost all tissues. It is found in greater concentrations in lymphoid tissue, especially in the thymus. This already indicates that inosine and deoxyinosine play a role in the immune system. This is particularly evident in the presence of a genetically caused ADA enzyme deficiency. The enzyme deficiency leads to an inhibition of B and T lymphocytes, so that lymphopenia, a pathologically conspicuous low concentration of lymphocytes in the blood, can develop. In addition, inosine is thought to have primarily antiviral effects. Another effect of inosine that is currently being discussed by experts is the influence of the nucleoside on the regeneration of nerve tissue after injuries or strokes. As a drug or dietary supplement, inosine is used to take advantage of its antiviral effects and to enhance performance during vigorous muscular activity. The performance-enhancing effect comes from increased formation of adenosine triphosphate (ATP), through which muscle cells obtain their energy. Inosine is also used in subacute sclerosing panencephalitis (SSPE) to halt the progression of the disease as far as possible. The disease, a form of inflammation of the CNS, is caused by a so-called slow virus infection with an extremely long incubation period, but shows a severe course during the acute phase. The effect of inosine in slowing PD is currently controversial.
Formation, occurrence, properties, and optimal values
Inosine can be synthesized by the body itself via purine metabolism or obtained by catalysis of adenosine-containing proteins. The adenosine obtained from catalysis is deaminated by the enzyme ADA and converted to inosine with cleavage from a water molecule. Despite the body’s ability to use inosine from its own production when needed, the nucleoside is present in many foods in appreciable concentrations, most notably in meat, meat extracts, household yeasts, and even sugar beets. An excess of inosine is metabolized by the purine breakdown process in the liver and degraded to uric acid, which is excreted mainly in the kidneys, but also to a lesser extent through sweat, saliva and the intestines.Inosine is often taken as a dietary supplement to increase muscular strength and the ability to concentrate. Since inosine hardly occurs in free form in the body and the concentration must adapt to rapidly changing requirements, there is no reference value as a measure of optimal supply. Excess insosine is completely broken down in the course of purine metabolism. At most, there may be an increased concentration of uric acid, which can lead to the formation of urinary stones.
Diseases and disorders
One of the major dangers associated with inosine deficiency is a genetic defect that causes deficiency of the enzyme ADA, an enzyme that deaminates adenosine and converts it to inosine with cleavage of a water molecule. The resulting deficiency of inosine has an inhibitory effect on the formation of lymphocytes, limiting the effectiveness of the immune system. The opposite of a deficiency, an oversupply, is largely compensated for by the body without any recognizable physiological effects. Only the uric acid level increases due to the high metabolism of inosine via the purine degradation process. Existing diseases such as gout may be exacerbated by the elevated uric acid level. It can also promote the formation of urinary stone conglomerates. Allergic skin reactions such as urticaria and erythema have also been observed due to the elevated uric acid level. Inosine should therefore not be taken as a drug or in the form of a dietary supplement in the presence of existing diseases such as gout, kidney stones, autoimmune diseases, and in cases of known pregnancy and during lactation (contraindications).