Chapter 20: Purine and Urate Metabolism

Purine and Urate Metabolism investigates the dual pathways of purine nucleotide synthesis, contrasting the de novo assembly from small molecules like glutamine and glycine with the critical salvage mechanisms involving enzymes such as hypoxanthine-guanine phosphoribosyl transferase (HGPRT). The narrative details the breakdown of adenine and guanine into uric acid, a process mediated by xanthine oxidase, which stands as the final metabolic product due to the human absence of the uricase enzyme. Significant emphasis is placed on the clinical repercussions of metabolic dysfunction, focusing on hyperuricaemia and its role in the development of gouty arthritis, where monosodium urate crystals precipitate in joints and soft tissues to form tophi. The sources categorize hyperuricaemia into primary genetic overproduction and secondary causes, including high cellular turnover in malignancies, renal excretion defects, and pharmacological triggers such as thiazide diuretics. Management strategies are explored, encompassing dietary modifications and the use of xanthine oxidase inhibitors like allopurinol alongside uricosuric agents to facilitate renal clearance. Finally, the chapter distinguishes gout from pseudogout—characterized by calcium pyrophosphate deposition—and addresses rare conditions like Lesch-Nyhan syndrome and hypouricaemia linked to xanthinuria or Fanconi’s syndrome.