Lecture Notes: Catecholamine Synthesis

Introduction

• Catecholamines: Compounds composed of a catechol (benzene with two hydroxyl groups) plus an amine group.
• Examples: Dopamine, norepinephrine, epinephrine.
• Functions: Act as neurotransmitters and hormones.
• Origins: Derived from phenylalanine and tyrosine (phenylalanine is essential; tyrosine is non-essential).

Synthesis Pathway

1. Phenylalanine to Tyrosine

   • Enzyme: Phenylalanine hydroxylase.
   • Reaction: Hydroxylation using tetrahydrobiopterin (THB), converting to dihydrobiopterin (DHB).
   • Note: DHB can be recycled to THB via dihydrobiopterin reductase with NADPH.
   • Significance: 50% of dietary phenylalanine is used for tyrosine synthesis.

2. Tyrosine to 3,4-Dihydroxyphenylalanine (DOPA)

   • Enzyme: Tyrosine hydroxylase.
   • Reaction: Hydroxylation using tetrahydrobiopterin (THB).

3. DOPA to Dopamine

   • Enzyme: Aromatic amino acid decarboxylase.
   • Cofactor: Vitamin B6 (pyridoxal phosphate).
   • Reaction: Decarboxylation (removal of CO2).

4. Dopamine to Norepinephrine

   • Reaction: Hydroxylation.
   • Enzyme: Requires Vitamin C (ascorbate), producing dehydroascorbate.

5. Norepinephrine to Epinephrine

   • Enzyme: Phenylethanolamine N-methyltransferase.
   • Cofactor: S-adenosylmethionine (SAM) donating a methyl group.
   • Reaction: Methylation; SAM converted to S-adenosylhomocysteine.

Genetic Disorders Related to Catecholamine Pathway

• Phenylketonuria (PKU): Mutation in phenylalanine hydroxylase, leading to high phenylalanine levels.
• Albinism: Mutation in tyrosinase, affecting melanin production.
• Dopamine β-hydroxylase deficiency: Affects dopamine to norepinephrine conversion.
• Vitiligo and Alzheimer's Disease: Potential links to phenylethanolamine N-methyltransferase activity.

Key Points Recap

• Pathway involves several key enzymes: phenylalanine hydroxylase, tyrosine hydroxylase, aromatic amino acid decarboxylase, and phenylethanolamine N-methyltransferase.
• Steps include hydroxylation, decarboxylation, methylation.
• Disorders may arise from enzyme mutations affecting the catecholamine synthesis pathway.

End of Lesson

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