Purine and Pyrimidine Bases Are Recycled by Salvage Pathways

Free purine and pyrimidine bases are constantly released in cells during the metabolic degradation of nu-cleotides. Free purines are in large part salvaged and reused to make nucleotides, in a pathway much simpler than the de novo synthesis of purine nucleotides described earlier. One of the primary salvage pathways consists of a single reaction catalyzed by adenosine phosphoribosyltransferase, in which free adenine reacts with PRPP to yield the corresponding adenine nucleotide:

Free guanine and hypoxanthine (the deamination product of adenine; Fig. 22-45) are salvaged in the same way by hypoxanthine-guanine phosphoribosyltransferase. A similar salvage pathway exists for pyrimidine bases in microorganisms, and possibly in mammals.

A genetic lack of hypoxanthine-guanine phos-phoribosyltransferase activity, seen almost exclusively in male children, results in a bizarre set of symptoms called Lesch-Nyhan syndrome. Children with this genetic disorder, which becomes manifest by the age of 2 years, are sometimes poorly coordinated and mentally retarded. In addition, they are extremely hostile and show compulsive self-destructive tendencies: they mutilate themselves by biting off their fingers, toes, and lips.

The devastating effects of Lesch-Nyhan syndrome illustrate the importance of the salvage pathways. Hy-poxanthine and guanine arise constantly from the breakdown of nucleic acids. In the absence of hypoxanthine-guanine phosphoribosyltransferase, PRPP levels rise and purines are overproduced by the de novo pathway, resulting in high levels of uric acid production and goutlike damage to tissue (see below). The brain is especially dependent on the salvage pathways, and this may account for the central nervous system damage in children with Lesch-Nyhan syndrome. This syndrome is another target of early trials in gene therapy (see Box 9-2). ■

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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