Biochemistry · Topic
Catecholamines: synthesis and breakdown !
Tyrosine becomes dopamine, noradrenaline and adrenaline in four steps; the adrenal medulla releases mostly adrenaline.
Updated 2026-11-01
Key facts
- Tyrosine → L-DOPA (tyrosine hydroxylase, rate-limiting, uses BH4) → dopamine (aromatic amino acid decarboxylase, uses B6) → noradrenaline (dopamine β-hydroxylase, uses vitamin C and copper) → adrenaline (PNMT, uses SAM).
- Adrenal medulla PNMT depends on the cortisol that reaches it through portal blood from the cortex.
- They are broken down by COMT and MAO: metanephrines and vanillylmandelic acid (VMA); dopamine gives homovanillic acid (HVA).
- Plasma free metanephrines are the most sensitive test for phaeochromocytoma.
In detail
- Tyrosine comes from the diet or from phenylalanine (phenylalanine hydroxylase). Tyrosine hydroxylase is activated by phosphorylation (PKA) during stress and held back by catecholamines.
- Dopamine enters vesicles through the VMAT transporter; inside the vesicle dopamine β-hydroxylase makes noradrenaline.
- In the chromaffin cell noradrenaline leaves for the cytosol, PNMT methylates it with S-adenosylmethionine and adrenaline returns to the vesicle; about 80 % of what the medulla releases is adrenaline.
- Release happens by exocytosis when acetylcholine from preganglionic sympathetic fibres stimulates the chromaffin cell.
- Action ends by neuronal reuptake and by COMT (liver, kidney, the chromaffin cell itself) and MAO (mitochondria).
Clinical notes
- Phaeochromocytoma: spells of headache, sweating and palpitations with hypertension; high metanephrines in plasma or urine.
- Childhood neuroblastoma: high urinary VMA and HVA.
- In Parkinson disease L-DOPA is given with a peripheral decarboxylase inhibitor so more reaches the brain.
- MAO inhibitors with tyramine-rich foods can trigger a hypertensive crisis.
Pathways
Related conditions
Related
- Tyrosine
- Tyrosine hydroxylase
- Tetrahydrobiopterin (BH4)
- S-adenosylmethionine (SAM)
- Adrenaline
- Cortisol
- Molecules derived from amino acids
- G protein-coupled receptors and cAMP
- Vitamin C (ascorbic acid)
- Copper
Test yourself
Think of the answer, then tap the question to see it.
What is the rate-limiting step of catecholamine synthesis, and which cofactor does it use?
Tyrosine hydroxylase, which uses tetrahydrobiopterin (BH4).
Why does the adrenal medulla make more adrenaline than other sympathetic tissues?
Because it receives concentrated cortisol from the cortex through the portal circulation, and cortisol induces PNMT.
Which vitamin and which metal does dopamine β-hydroxylase need?
Vitamin C (ascorbate) and copper.
Which metabolites are measured to look for a phaeochromocytoma?
Plasma free metanephrines or urinary fractionated metanephrines.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Catecholamine blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); PNMT: Phenylethanolamine N-methyltransferase (human) (UniProt, 2026); DBH: Dopamine beta-hydroxylase (human) (UniProt, 2026); COMT: Catechol O-methyltransferase (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.