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# 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

- [Phenylalanine and tyrosine metabolism](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/)
- [Catecholamine synthesis and breakdown](https://durgical.com/en/biochemistry/pathways/catecholamine-synthesis-and-breakdown/)

## Related conditions

- [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/)
- [Hereditary paraganglioma and pheochromocytoma (SDH)](https://durgical.com/en/conditions/hereditary-paraganglioma-and-pheochromocytoma/)
- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)
- [Anaphylaxis](https://durgical.com/en/conditions/anaphylaxis/)

## Related

- [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/)
- [Tyrosine hydroxylase](https://durgical.com/en/biochemistry/enzymes/tyrosine-hydroxylase/)
- [Tetrahydrobiopterin (BH4)](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/)
- [S-adenosylmethionine (SAM)](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/)
- [Adrenaline](https://durgical.com/en/biochemistry/molecules/adrenaline/)
- [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/)
- [Molecules derived from amino acids](https://durgical.com/en/biochemistry/topics/molecules-derived-from-amino-acids/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Vitamin C (ascorbic acid)](https://durgical.com/en/biochemistry/molecules/vitamin-c/)
- [Copper](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Catecholamine blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003561.htm) (MedlinePlus, US National Library of Medicine, 2026); [PNMT: Phenylethanolamine N-methyltransferase (human)](https://www.uniprot.org/uniprotkb/P11086/entry) (UniProt, 2026); [DBH: Dopamine beta-hydroxylase (human)](https://www.uniprot.org/uniprotkb/P09172/entry) (UniProt, 2026); [COMT: Catechol O-methyltransferase (human)](https://www.uniprot.org/uniprotkb/P21964/entry) (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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