| Degradation of purines in humans to uric acid
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Each of the purine monophosphates (IMP, AMP, XMP, and GMP) can be converted into their corresponding nucleosides by 5'-nucleotidase. The enzyme, purine nucleoside phosphorylase,
then converts the purine nucleoside (inosine, xanthosine or guanosine) into free purine base. This enzyme, however, does not function on adenosine . Two other enzymes, AMP deaminase and adenosine deaminase, convert the amino group of AMP and adenosine into the carbonyl group of IMP and inosine respectively.
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| LESCH-NYHAN SYNDROME RESULTS FROM HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE (HGPRT) DEFICIENCY |
| The gene encoding HGPRT is located on the X chromosome. Its deficiency results in a rare, X-linked recessive disorder termed Lesch-Nyhan syndrome. The lack of HGPRT causes an over-accumulation of PRPP, which is also the substrate for the enzyme amidophosphoribosyl transferase (see Fig. 29.2). This stimulates purine biosynthesis by up to 200-fold. Because of increased purine synthesis, the degradation product, uric acid, also accumulates to high levels. Elevated uric acid leads to a crippling gouty arthritis and severe neuropathology resulting in mental retardation, spasticity, aggressive behavior, and a compulsion towards self-mutilation by biting and scratching. |
| Once the various free bases have been formed, they are catabolized to the common base xanthine. The enzyme guanine deaminase converts the amino group of guanine into a carbonyl group, yielding xanthine. Xanthine oxidase (XO) oxidizes hypoxanthine, the free base derived from adenine via inosine, to xanthine, and this same enzyme oxidizes xanthine to uric acid (Fig. 29.4). Uric acid is the final
metabolic product of purine catabolism in primates, birds, reptiles, and many insects. Other organisms, including most mammals, fish, amphibians, and invertebrates metabolize uric acid to simpler forms.
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