Inosine

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. It was discovered in 1965 in analysis of RNA transferase. 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. 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 granulomatosis with polyangiitis 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 inosine monophosphate dehydrogenase (IMD) inhibition. 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 nucleotide reactions required for muscle movements. 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).