Hypoxanthine

Hypoxanthine is a base found in an intermediate of purine nucleotide biosynthesis. Figure 22.4 summarizes the pathway leading from phosphoribosyl-1-pyrophosphate (PRPP) to the first fully formed purine nucleotide, inosine 5'-monophosphate (IMP), also called inosinic acid. IMP contains as its base, hypoxanthine.

Hypoxanthine is also a product of catabolism of purine nucleotides (Figure 22.7). Hypoxanthine can be converted to xanthine by the enzyme xanthine oxidase in the reaction that follows:

Hypoxanthine + O 2 <=> Xanthine + H 2 O 2

In addition, hypoxanthine can be converted back to IMP in purine nucleotide salvage biosynthesis (by the enzyme HGPRT), as shown in Figure 22.9.

Complete deficiency of HGPRT results in gout-related arthritis, dramatic malfunction of the nervous system, behavioral disorders, learning disability, and hostile or aggressive behavior, often self directed. In the most extreme cases, patients nibble at their fingertips or, if restrained, their lips, causing severe self-mutilation.

Allopurinol, which is similar to hypoxanthine (see here), is used to treat gout because it inhibits xanthine oxidase, leading to accumulation of hypoxanthine and xanthine, both of which are more soluble and more readily excreted than uric acid, the chemical that causes gout.

See also: De Novo Biosynthesis of Purine Nucleotides, Purine Degradation, Excessive Uric Acid in Purine Degradation, Salvage Routes to Deoxyribonucleotide Synthesis, Nucleotide Analogs in Selection

INTERNET LINKS:

> 1. Purine Metabolism

> 2. Purine and Pyrimidine Metabolism