Heme Synthesis Pathway and Associated Diseases

Introduction

• Presenter: Dirty Medicine
• Topic: Heme synthesis pathway
• Focus:
  • Understanding pathway components: products, reactants, enzymes
  • Identifying diseases associated with enzyme deficiencies
  • Simplifying learning with mnemonics

Overview of Heme Synthesis Pathway

• Location:
  • Part occurs in the mitochondria
  • Part occurs in the cytosol
• Reactants and Products:
  • Start: Glycine + Succinyl CoA
  • Product: Aminolevulinic acid (ALA) via ALA Synthase (rate-limiting step)
  • Vitamin B6 as a cofactor

Pathway Steps

1. Mitochondria:
   • Glycine + Succinyl CoA → ALA
   • ALA leaves mitochondria to cytosol
2. Cytosol:
   • ALA → Porphobilinogen (via ALA Dehydratase)
   • Porphobilinogen → Hydroxymethylbiline (via Porphobilinogen Deaminase)
   • Hydroxymethylbiline → Uroporphyrinogen III
   • Uroporphyrinogen III → Coproporphyrinogen III (via Uroporphyrinogen Decarboxylase)
3. Back to Mitochondria:
   • Coproporphyrinogen III → Protoporphyrin
   • Protoporphyrin → Heme (via Ferrochelatase, using iron as a cofactor)

Mnemonics for Memorization

• Transition Points:
  • ALA: "I'm going ALA Cytosol" (ALA goes to the cytosol)
  • Coproporphyrinogen: "Cop me some mitochondria" (Coproporphyrinogen goes to the mitochondria)
• Pathway Order: G S A P H U C P H
  • "Get Some Additional Points Having Understood the Correct Pathway for Heme"

Diseases Associated with Enzyme Deficiencies

1. ALA Synthase Deficiency:

   • Disease: Sideroblastic Anemia
   • Cause: Congenital (X-linked) or Acquired (B6 deficiency, alcoholism, lead poisoning)
   • Associations: Ringed sideroblasts, iron overload labs
   • Mnemonic: SA (Sideroblastic Anemia) backwards is AS (ALA Synthase)

2. ALA Dehydratase & Ferrochelatase Deficiency:

   • Disease: Lead Poisoning
   • Causes: Environmental exposure (e.g., lead paint, batteries)
   • Associations:
     • Basophilic stippling
     • Lead lines in bones
     • Burton lines in gums
   • Mnemonic: LEAD from "Lyrochelatase" (Ferrochelatase) and AD (ALA Dehydratase)

3. Porphobilinogen Deaminase Deficiency:

   • Disease: Acute Intermittent Porphyria
   • Symptoms: GI pain, neuropathy, psychological symptoms
   • Triggers: P450 inducers (e.g., phenytoin)
   • Mnemonic: AIPD for Acute Intermittent Porphyria, Deaminase

4. Uroporphyrinogen Decarboxylase Deficiency:

   • Disease: Porphyria Cutanea Tarda
   • Symptoms: Hyperpigmentation, blistering, photosensitivity
   • Associations: Hepatitis C, alcohol use
   • Treatment: Phlebotomy, hydroxychloroquine

Conclusion

• Keep study methods simple and use mnemonics
• Understanding the heme synthesis pathway and related diseases can help in medical exams
• Share knowledge to help others avoid expensive resources

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This guide provides a concise review of the heme synthesis pathway, its enzymes, and the diseases associated with enzyme dysfunction, alongside useful mnemonics for memorization and understanding.