De Novo Purine Synthesis and Salvage Pathway

De Novo Purine Synthesis

• Occurs in the liver, kidneys, and other tissues
• Synthesizes inosine monophosphate (IMP) from ribose-5-phosphate and amino acids
• IMP is the precursor to adenosine and guanosine nucleotides
• Enzymes involved:
  • PRPP synthetase (converts ribose-5-phosphate to phosphoribosylpyrophosphate)
  • Glutamine phosphoribosylpyrophosphate amidotransferase (converts phosphoribosylpyrophosphate to IMP)

Purine Salvage Pathway

• Recycles purine bases and nucleosides to form nucleotides
• Enzymes involved:
  • Adenine phosphoribosyltransferase (converts adenine to AMP)
  • Hypoxanthine-guanine phosphoribosyltransferase (converts hypoxanthine and guanine to IMP and GMP)
• Occurs in the liver, kidneys, and other tissues
• Important for maintaining purine nucleotide levels and preventing uric acid accumulation

Adenosine Metabolism

• Adenosine is a signaling molecule involved in sleep, pain, and inflammation
• Metabolized by adenosine deaminase to inosine
• Adenosine receptors (A1, A2A, A2B, A3) mediate its effects on the body
• Adenosine is a vasodilator and has anti-inflammatory properties

Xanthine Oxidase Function

• Converts hypoxanthine to xanthine and xanthine to uric acid
• Found in the liver, kidneys, and small intestine
• Inhibitors of xanthine oxidase (e.g., allopurinol) are used to treat gout and hyperuricemia
• Xanthine oxidase also generates reactive oxygen species (ROS), contributing to oxidative stress

Purine Nucleotide Cycle

• A metabolic pathway that interconverts AMP, IMP, and GMP
• Involved in regulating energy metabolism, particularly in muscle tissue
• Enzymes involved:
  • Adenylate kinase (converts AMP to ADP)
  • Adenylosuccinate synthase (converts IMP to AMP)
  • GMP synthase (converts IMP to GMP)
• Plays a role in maintaining energy homeostasis and regulating muscle contraction