Hypoxanthin

Hypoxanthin, commonly referred to as hypoxanthine, is a naturally occurring purine base and a 6-oxopurine. It is formed by deamination of adenine and can exist free in solution or as part of nucleosides such as inosine (hypoxanthine attached to ribose via N9).

Biological role: In purine metabolism, hypoxanthin is a central intermediate. In the purine salvage pathway, hypoxanthin is converted to inosine monophosphate (IMP) by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using phosphoribosyl pyrophosphate (PRPP). Salvage minimizes de novo synthesis and conserves energy.

In catabolism, hypoxanthin is oxidized by xanthine oxidoreductase to xanthine and then to uric acid, which is excreted in humans. This pathway is a major source of uric acid, and excessive production or impaired excretion can lead to hyperuricemia and gout.

Occurrence: Hypoxanthin is found in many organisms and occurs as a free base, and as part of nucleotides and nucleosides, notably inosine and IMP, across tissues.

Clinical significance: Genetic deficiency of HGPRT causes Lesch-Nyhan syndrome, with impaired purine salvage, elevated de novo synthesis, and increased uric acid production. Abnormal hypoxanthin metabolism can be detected in metabolic disorders using urinary or plasma analysis.

Analytical methods: Hypoxanthin can be measured by HPLC, enzymatic assays, or mass spectrometry in biological samples.