39. Biosynthesis and degradation of purine nucleotides. Regulation of purine nucleotides biosynthesis. Tissue specificity. Hyperuricemia and gout. Inhibition of xanthine oxidase. Enzyme defects in the metabolism of purine nucleotides (immune deficiencies, Lesch-Nyhan syndrome, gout). Purine analogues used as anticancer and antiviral drugs.

INTRODUCTION

Purines are organic compounds that are integral to the structure and function of genetic material (DNA and RNA) and play critical roles in cellular processes. They are composed of a double-ring structure, with one ring being a pyrimidine and the other an imidazole. Adenine and guanine are the two primary purines found in nucleic acids. These molecules are essential for storing and transferring energy within cells, serving as components of important cellular messengers like ATP and GTP, and participating in metabolic pathways.

BIOSYNTHESIS AND DEGRADATION OF PURINE NUCLEOTIDES:

Biosynthesis:

• Purine nucleotides are essential building blocks for DNA and RNA synthesis.
• Biosynthesis occurs through the de novo and salvage pathways.
• De novo synthesis: Occurs in the cytoplasm and involves the step-by-step assembly of purine nucleotides from simple precursors.
• Salvage pathway: Utilizes preformed purine bases (hypoxanthine, guanine) salvaged from the degradation of nucleic acids or dietary sources.
• Key enzymes involved in de novo synthesis include amidophosphoribosyltransferase (PRPP amidotransferase), phosphoribosylglycinamide synthetase, phosphoribosylformylglycinamidine synthase, and others.
• Salvage pathway enzymes include hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT).