inosine
Definition: Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N9-glycosidic bond. Inosine is commonly found in tRNAs and is essential for proper translation of the genetic code in wobble base pairs.
Knowledge of inosine metabolism has led to advances in immunotherapy in recent decades.
Inosine monophosphate is oxidised by the enzyme inosine monophosphate dehydrogenase, yielding xanthosine monophosphate, a key precursor in purine metabolism.
Metabolism
Adenine is converted to adenosine or inosine monophosphate (IMP), either of which, in turn, is converted into inosine (I), which pairs with Adenine (A), cytosine (C), and uracil (U).
Purine nucleoside phosphorylase intraconverts inosine and hypoxanthine.
Inosine is also an intermediate in a chain of purine nucleotides reactions required for muscle movements.
Biotechnology
When designing primers for polymerase chain reaction, 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.
Therapeutics
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 diseases including Wegener granulomatosis because the uptake of purine by actively dividing B cells 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.
References
Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing. Wulff BE, Sakurai M, Nishikura K. Nat Rev Genet. 2011 Feb;12(2):81-5. PMID: #21173775#