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

3. DOPA to Dopamine

   • Enzyme: DOPA decarboxylase

4. Dopamine to Norepinephrine

   • Enzyme: Dopamine beta-hydroxylase

5. 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