phosphoribosyl pyrophosphate
Summary
Phosphoribosyl pyrophosphate (PRPP) is a key regulatory molecule in purine and pyrimidine nucleotide synthesis. It serves as the activated ribose donor in the de novo purine synthesis pathway and salvage pathways. PRPP synthetase deficiency or overactivity can lead to immunodeficiency or gout, respectively.
Detail
Phosphoribosyl pyrophosphate (PRPP) is synthesized from ribose-5-phosphate and ATP by the enzyme PRPP synthetase. It plays crucial roles in nucleotide metabolism: (1) In de novo purine synthesis, PRPP combines with glutamine via glutamine PRPP amidotransferase to form 5-phosphoribosyl-1-amine, the first committed step. (2) In salvage pathways, PRPP reacts with purine bases (adenine, guanine, hypoxanthine) via phosphoribosyltransferases (APRT, HPRT) to regenerate nucleotides efficiently. (3) PRPP is also required for pyrimidine nucleotide synthesis and histidine/tryptophan biosynthesis. Clinical significance includes PRPP synthetase superactivity causing gout due to purine overproduction, and PRPP synthetase deficiency leading to combined immunodeficiency due to impaired lymphocyte DNA synthesis. HPRT deficiency (Lesch-Nyhan syndrome) results in PRPP accumulation and subsequent purine overproduction.
Sources
- Lippincott Illustrated Reviews: Biochemistry
- First Aid for the USMLE Step 1
- Lehninger Principles of Biochemistry
- Medical Biochemistry by Baynes & Dominiczak
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