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Understanding Catecholamine Synthesis Pathway

Apr 12, 2025

Biochemistry Lecture: Catecholamine Synthesis

Introduction

  • High yield topic: Catecholamine Synthesis
  • Catecholamines: Dopamine, Norepinephrine, Epinephrine
  • Synthesized in:
    • Chromophane cells of adrenal medulla
    • Postganglionic fibers of sympathetic nervous system
  • Function: Neurotransmission and sympathetic transmission in the adrenal axis

Biochemical Pathway of Catecholamine Synthesis

  1. Phenylalanine to Tyrosine

    • Enzyme: Phenylalanine hydroxylase
      • Converts phenylalanine to tyrosine
  2. Tyrosine to DOPA

    • Enzyme: Tyrosine hydroxylase
      • Converts tyrosine to DOPA

Mnemonic Introduction

  • Game of Thrones based mnemonic
  • Focus: Tyrion Lannister (Peter Dinklage)
    • Smartest character, similar to neurotransmitter function in the brain

Mnemonic Breakdown

  • Peter Dinklage Plays Tyrion, Who is a Dope Character
    • P for Phenylalanine
    • Tyr for Tyrosine
    • Dope for DOPA

Side Pathways

  1. Tyrosine's Side Pathway

    • Tyrosine to Homogentisic Acid (enzyme not important)
      • Converts to Maleyl Acetoacetic Acid to Fumarate (Enters TCA Cycle)
    • Enzyme: Homogentisate Oxidase
      • Disease: Alkaptonuria
        • Autosomal recessive
        • Symptoms: Pigment deposition (blue-black), dark urine, arthralgia
  2. DOPA's Side Pathway

    • DOPA to Melanin
    • Enzyme: Tyrosinase
      • Disease: Albinism
        • Autosomal recessive
        • Symptoms: White skin/hair, blue eyes, decreased visual acuity, increased skin cancer risk
        • Normal melanocytes, decreased melanin production

Continuation of Pathway

  1. DOPA to Dopamine

    • Enzyme: DOPA decarboxylase
  2. Dopamine to Norepinephrine

    • Enzyme: Dopamine beta-hydroxylase
  3. Norepinephrine to Epinephrine

    • Enzyme: Phenylethanolamine N-methyltransferase

Mnemonic Completed

  • Without Tyrion, Game of Thrones could do No Episodes
    • Do for Dopamine
    • No for Norepinephrine
    • Episodes for Epinephrine

Important Cofactors

  • Phenylalanine to Tyrosine: BH4
  • Tyrosine to DOPA: BH4
  • DOPA to Dopamine: B6
  • Dopamine to Norepinephrine: Vitamin C
  • Norepinephrine to Epinephrine: SAM

Diseases Related to Pathway Disruptions

  1. Phenylketonuria (PKU)
    • Deficiency: Phenylalanine hydroxylase or BH4
    • Symptoms: Musty odor, growth restriction, eczema, epilepsy
    • Treatment: Increase tyrosine intake, decrease phenylalanine intake
    • Avoid aspartame (contains phenylalanine)

Summary

  • Remember the catecholamine synthesis pathway: Phenylalanine → Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine
  • Use the mnemonic to remember the order and diseases
  • Focus on enzyme deficiencies and symptoms for exams