Purine Synthesis

• Salvage
  • Adenine + PRPP <=> Adenylate + PPi (Adenine phosphoribosyl transferase)
  • Guanine + PRPP <=> Guanylate + PPi (Hypoxanthine-guanine phosphoribosyltransferase - HGPRT)
  • Hypoxanthine + PRPP <=> Inosinate + PPi (HGPRT) HERE
• de novo scheme (Figure 25.5)
• Reactions 1-6 (Figure 25.6)
• Inosinate formation (Figure 25.7)
• Making AMP & GMP (Figure 25.8)

dNTP Synthesis

Ribonucleotide reductase

• Action scheme (Unnumbered, p. 718 HERE)
• Overall structure - R1 dimer + R2 dimer (Figure 25.9)
• R2 subunit (Figure 25.10)
• Reaction mechanism (Figure 25.11)
• Thymidylate synthesis (Figure 25.12)
• Dihydrofolate reductase (Unnumbered, p. 721)
• Anticancer drug targets (Figure 25.13)
• Suicide inhibition (Figure 25.14)
• Aminopterin/Methotrexate (Unnumbered, p. 723 HERE)
• Trimethoprim (Unnumbered, p. 723 HERE)

Nucleotide Synthesis Regulation

• ATCase feedback inhibition of pyrimidine synthesis (Unnumbered, p. 723 HERE)
• Control of purine synthesis (Figure 25.15)
• Regulation of dNTP synthesis by ribonucleotide reductase (Figure 25.16 HERE and HERE)

Nucleotide catabolism

• SCID and adenosine deaminase deficiency (Figure 25.17)
• Hypoxanthine -> xanthine -> uric acid (Gout) (Figure 25.18)
  • Allopurinol treatment
    • Suicide inhibitor of xanthine oxidase
• Lesch-Nyhan syndrome
  • Deficiency of Hypoxanthine-guanine phosphoribosyltransferase - HGPRT and accumulation of PRPP and urate
• Folic acid deficiency promotes spinal bifida
  • 70% reduction when supplemented in mother's diet