Biochemistry Series: Catecholamine Synthesis

Introduction

• This lecture covers catecholamine synthesis, focusing on dopamine, norepinephrine, and epinephrine.
• Catecholamines are neurotransmitters in the sympathetic nervous system, synthesized in the adrenal medulla's chromophane cells and sympathetic postganglionic fibers.
• Key focus on biochemical pathways and diseases from pathway disruptions.

Catecholamine Synthesis Pathway

Starting Point

• Begins with the amino acid Phenylalanine.
• Phenylalanine is converted to Tyrosine by the enzyme Phenylalanine Hydroxylase.

Enzymatic Pathway

1. Phenylalanine → Tyrosine (Enzyme: Phenylalanine Hydroxylase)
2. Tyrosine → DOPA (Enzyme: Tyrosine Hydroxylase)
3. DOPA → Dopamine (Enzyme: DOPA Decarboxylase)
4. Dopamine → Norepinephrine (Enzyme: Dopamine Beta Hydroxylase)
5. Norepinephrine → Epinephrine (Enzyme: Phenylethanolamine N-methyltransferase)

Mnemonic

• Peter Dinklage plays Tyrion who is a dope character, so Game of Thrones could do no episodes:
  • P: Phenylalanine
  • TYR (Tyrion): Tyrosine
  • DOPE: DOPA
  • DO: Dopamine
  • NO: Norepinephrine
  • EPISODES: Epinephrine

Diseases Related to Pathway Disruptions

Alkaptonuria

• Caused by knockout of Homogentisate Oxidase.
• Leads to buildup of Homogentisic Acid, a pigment.
• Symptoms: Pigment deposition (bluish-black) in ears, hands, sclera, dark urine, arthralgias.
• Inheritance: Autosomal Recessive

Albinism

• Caused by knockout of Tyrosinase or issues in tyrosine transport.
• Leads to decreased melanin production (normal number of melanocytes).
• Symptoms: White skin/hair, blue eyes, decreased visual acuity, increased skin cancer risk.
• Association: Chediak-Higashi syndrome

Phenylketonuria (PKU)

• Caused by deficiency of Phenylalanine Hydroxylase or cofactor BH4.
• Causes phenylalanine buildup and decreased tyrosine.
• Symptoms: Musty odor, growth restriction, eczema, epilepsy.
• Treatment: Increase dietary tyrosine, decrease phenylalanine, avoid aspartame.

Cofactors in Catecholamine Synthesis

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

Summary

• Catecholamine synthesis is a crucial biochemical pathway involving phenylalanine, tyrosine, DOPA, dopamine, norepinephrine, and epinephrine.
• Understanding the pathway and related diseases is essential for exams.
• Use the mnemonic and disease associations to remember key concepts.