hypoxanthine

Hypoxanthine is a naturally occurring purine base and a key intermediate in nucleotide metabolism. It is classified as a 6-oxopurine and forms inosine when linked to ribose at the N9 position. In biological systems, hypoxanthine is a central product of purine catabolism and a substrate in nucleotide salvage.

In purine degradation, adenine is deaminated to hypoxanthine, which can be further oxidized by xanthine oxidoreductase to xanthine and then to uric acid. This pathway helps regulate purine levels and uric acid production. In parallel, the salvage pathway recovers purine bases: hypoxanthine combines with phosphoribosyl pyrophosphate (PRPP) under the action of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to form inosine monophosphate (IMP), which can then enter nucleotide pools.

Hypoxanthine is also the base component of inosine, the ribonucleoside formed by attaching hypoxanthine to a ribose sugar. In RNA, inosine is produced by deamination of adenosine and is important for wobble-base pairing in certain tRNAs, allowing flexible recognition of codons.

Clinical relevance includes the salvage pathway: defects in HGPRT, as seen in Lesch-Nyhan syndrome, disrupt purine salvage and elevate uric acid levels. Hypoxanthine and its metabolites can be measured in biological samples to assess purine metabolism, renal function, and related disorders. Hypoxanthine is present in cells from normal metabolism and also occurs in dietary sources containing purines.