Purine Salvage Pathway and Lesch-Nyhan Syndrome

Overview of Purine Salvage

• Purine Salvage is a biochemical pathway that recycles purine bases into purine nucleotides.
  • Essential for the body's ability to create necessary molecules.
  • Allows for seamless operations between purine salvage and synthesis.

Starting Points for Purine Salvage

• Free bases involved:
  • Guanine
  • Hypoxanthine
  • Adenine

Key Enzymes and Reactions

HGPRT (Hypoxanthine Guanine Phosphoribosyltransferase)

• Converts:
  • Guanine into GMP (Guanosine Monophosphate)
  • Hypoxanthine into IMP (Inosine Monophosphate)
• Extremely important enzyme for purine salvage.

APRT (Adenine Phosphoribosyltransferase)

• Converts Adenine into AMP (Adenosine Monophosphate).

Clinical Relevance

Lesch-Nyhan Syndrome

• Caused by HGPRT deficiency:
  • Leads to an inability to recycle guanine and hypoxanthine back into GMP and IMP.
  • Results in increased conversion of guanine and hypoxanthine into xanthine.
  • Xanthine is then converted into uric acid by xanthine oxidase.
• Symptoms:
  • Intellectual disability
  • Self-mutilation
  • Aggression
  • Sodium urate crystals in urine (appear orange)
  • Gout
  • Dystonia
• Inheritance: X-linked recessive.

Treatment of Lesch-Nyhan Syndrome

• Allopurinol: Inhibits xanthine oxidase to prevent uric acid buildup.
• Alternative: Febuxostat if allopurinol cannot be used.

Exam Tips for USMLE and COMLEX

• Recognizing clinical presentations:
  • Symptoms like intellectual disability, self-mutilation, and visible sodium urate crystals.
  • Description might include images of diapers with orange spots indicating sodium urate crystals.
• Remember the biochemical pathway disruptions and their clinical implications.

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These notes cover all critical aspects of purine salvage pathways, focusing on HGPRT's role, the biochemistry, the clinical presentation of Lesch-Nyhan syndrome, and relevant treatments.