Purine Synthesis and Salvage Pathway

De Novo Purine Synthesis

• Occurs in the cytosol of cells
• Two stages: synthesis of inosine monophosphate (IMP) and conversion of IMP to AMP and GMP
• Key enzymes:
  • PRPP synthetase (generates phosphoribosyl pyrophosphate (PRPP))
  • Glutamine phosphoribosyl pyrophosphate amidotransferase (converts PRPP to IMP)
• Regulation: feedback inhibition by AMP and GMP, allosteric inhibition by ATP

Purine Salvage Pathway

• Recycles free purine bases (adenine, guanine, and hypoxanthine) to form nucleotides
• Two key enzymes:
  • Adenosine kinase (converts adenine to AMP)
  • Hypoxanthine-guanine phosphoribosyltransferase (converts hypoxanthine and guanine to IMP and GMP, respectively)
• Importance: conserves energy and reduces the need for de novo synthesis

Adenosine Metabolism

• Adenosine is a signaling molecule involved in various physiological processes
• Metabolism:
  • Deaminated to inosine by adenosine deaminase
  • Converted to AMP by adenosine kinase
  • Broken down to inosine and ammonia by adenosine deaminase
• Importance: adenosine receptor signaling plays a role in regulating cardiac function, pain perception, and inflammation

Purine Nucleotide Cycle

• A metabolic pathway that interconverts AMP, ADP, and ATP
• Key enzymes:
  • Adenylate kinase (converts AMP to ADP and ATP)
  • Adenosine monophosphate deaminase (converts AMP to IMP)
• Importance: regulates the balance of adenine nucleotides in cells

Xanthine Oxidase Function

• A key enzyme in the degradation of purines to uric acid
• Catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid
• Inhibition: allopurinol (used to treat gout and hyperuricemia)

Disorders of Purine Metabolism

• Gout: Characterized by hyperuricemia, uric acid crystal deposition, and joint inflammation
• Lesch-Nyhan syndrome: A genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase, leading to excess uric acid production and neurological symptoms
• Adenosine deaminase deficiency: A genetic disorder characterized by immunodeficiency and increased susceptibility to infections
• Purine nucleoside phosphorylase deficiency: A genetic disorder characterized by immunodeficiency and neurological symptoms

This quiz covers the processes of de novo purine synthesis and the purine salvage pathway, including key enzymes and regulation mechanisms.