[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Catecholamine synthesis and breakdown [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Catecholamine synthesis and breakdown The adrenal medulla and some neurons build dopamine, norepinephrine and epinephrine from tyrosine, then break them down to metanephrines and VMA. Updated 2026-11-01 ## Interactive map ## Key facts - Tyrosine hydroxylase is the rate-limiting step; it needs BH4, Fe²⁺ and O₂ and is inhibited by its own catecholamine products. - DOPA decarboxylase (vitamin B6) is the target of carbidopa, which stops levodopa from being decarboxylated outside the brain. - Dopamine β-hydroxylase works inside the storage vesicles and needs copper and vitamin C. - PNMT is found mainly in the adrenal medulla, where cortisol arriving from the cortex through portal blood induces it. - COMT makes metanephrines, and MAO plus aldehyde dehydrogenase make VMA; plasma free metanephrines are the screening test for phaeochromocytoma. **Also called** Dopamine, norepinephrine and epinephrine synthesis ## Regulation - Nerve impulses and stress activate tyrosine hydroxylase by phosphorylation (PKA, CaMK) within minutes and by making more enzyme over hours. - Dopamine and norepinephrine inhibit tyrosine hydroxylase by competing with BH4 (feedback). - Cortisol from the adrenal cortex induces PNMT, so epinephrine is made almost only in the adrenal medulla. ## The steps, one by one - **Step 1 · [Tyrosine hydroxylase (TH)](https://durgical.com/en/biochemistry/enzymes/tyrosine-hydroxylase/)** irreversible [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/) + [Tetrahydrobiopterin](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/) + o2 → [L-DOPA](https://durgical.com/en/biochemistry/molecules/l-dopa/) + Dihydrobiopterin (BH2) + H₂O Adds a hydroxyl to the ring of tyrosine to make L-DOPA; it is the slowest and most tightly controlled step. **If it fails:** Tyrosine hydroxylase deficiency: dopa-responsive dystonia or severe infantile parkinsonism; BH4 deficiencies also slow this step. - **Step 2 · Aromatic L-amino acid decarboxylase (AADC, DOPA decarboxylase)** irreversible [L-DOPA](https://durgical.com/en/biochemistry/molecules/l-dopa/) → [Dopamine](https://durgical.com/en/biochemistry/molecules/dopamine/) + CO₂ Removes the carboxyl group of L-DOPA to give dopamine; the same enzyme makes serotonin from 5-hydroxytryptophan. **If it fails:** Parkinson treatment depends on this step: brain AADC turns levodopa into dopamine while carbidopa blocks it outside the brain. AADC deficiency itself causes infantile hypotonia and oculogyric crises. [Parkinson disease →](https://durgical.com/en/conditions/parkinson-disease/) - **Step 3 · Dopamine β-hydroxylase (DBH)** irreversible [Dopamine](https://durgical.com/en/biochemistry/molecules/dopamine/) + [Vitamin C](https://durgical.com/en/biochemistry/molecules/vitamin-c/) + o2 → [Norepinephrine](https://durgical.com/en/biochemistry/molecules/norepinephrine/) + Dehydroascorbate + H₂O Inside the storage vesicles it adds a hydroxyl to the side chain of dopamine, giving norepinephrine. **If it fails:** DBH deficiency: no norepinephrine or epinephrine, with severe orthostatic hypotension; in Menkes disease low copper lowers DBH activity. [Menkes disease →](https://durgical.com/en/conditions/menkes-disease/) - **Step 4 · Phenylethanolamine N-methyltransferase (PNMT)** irreversible [Norepinephrine](https://durgical.com/en/biochemistry/molecules/norepinephrine/) + [S-adenosylmethionine](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/) → [Epinephrine (adrenaline)](https://durgical.com/en/biochemistry/molecules/adrenaline/) + [S-Adenosylhomocysteine](https://durgical.com/en/biochemistry/molecules/s-adenosylhomocysteine/) Moves a methyl group from SAM onto the amine of norepinephrine to give epinephrine, mainly in the adrenal medulla. **If it fails:** When cortisol is low, as in adrenal insufficiency, PNMT falls and the adrenal medulla makes less epinephrine. [Adrenal insufficiency →](https://durgical.com/en/conditions/adrenal-insufficiency/) - **Step 5 · Catechol-O-methyltransferase (COMT)** irreversible [Epinephrine (adrenaline)](https://durgical.com/en/biochemistry/molecules/adrenaline/) + [S-adenosylmethionine](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/) → Metanephrine + [S-Adenosylhomocysteine](https://durgical.com/en/biochemistry/molecules/s-adenosylhomocysteine/) Methylates the 3-hydroxyl of the catechol ring; inside tumour cells this makes metanephrine all the time. **If it fails:** Phaeochromocytomas contain COMT and leak metanephrines into the blood continuously, even between attacks of hypertension. [Phaeochromocytoma →](https://durgical.com/en/conditions/phaeochromocytoma/) - **Step 6 · Monoamine oxidase A, then aldehyde dehydrogenase** irreversible Metanephrine + o2 + H₂O + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) → Vanillylmandelic acid (VMA) + nh3 + NADH MAO removes the amine as ammonia and hydrogen peroxide, and aldehyde dehydrogenase oxidises the aldehyde to VMA, which leaves in the urine. **If it fails:** Urinary VMA and metanephrines rise in phaeochromocytoma and, in children, in neuroblastoma. ## Clinical notes - Parkinson disease: dopaminergic neurons of the substantia nigra are lost; levodopa with carbidopa replaces dopamine in the brain. - Phaeochromocytoma: a chromaffin-cell tumour that releases catecholamines; it is diagnosed with plasma or urine metanephrines. - Metyrosine inhibits tyrosine hydroxylase and is used to block catecholamine synthesis before surgery for phaeochromocytoma. - MAO inhibitors taken with tyramine-rich foods can cause a hypertensive crisis. ## Pathways - [Catecholamine synthesis and breakdown](https://durgical.com/en/biochemistry/pathways/catecholamine-synthesis-and-breakdown/) ## Related conditions - [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/) - [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/) - [Phenylketonuria (PKU)](https://durgical.com/en/conditions/phenylketonuria/) - [Menkes disease](https://durgical.com/en/conditions/menkes-disease/) ## 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/) - [L-DOPA (levodopa)](https://durgical.com/en/biochemistry/molecules/l-dopa/) - [Dopamine](https://durgical.com/en/biochemistry/molecules/dopamine/) - [Norepinephrine (noradrenaline)](https://durgical.com/en/biochemistry/molecules/norepinephrine/) - [Phenylalanine and tyrosine metabolism](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/) - [S-adenosylmethionine (SAM)](https://durgical.com/en/biochemistry/molecules/s-adenosylmethionine/) - [S-Adenosylhomocysteine (SAH)](https://durgical.com/en/biochemistry/molecules/s-adenosylhomocysteine/) - [Vitamin C (ascorbic acid)](https://durgical.com/en/biochemistry/molecules/vitamin-c/) - [Copper](https://durgical.com/en/biochemistry/topics/copper/) - [Vitamin B6 (pyridoxal phosphate)](https://durgical.com/en/biochemistry/molecules/vitamin-b6/) - [Molecules derived from amino acids](https://durgical.com/en/biochemistry/topics/molecules-derived-from-amino-acids/) - [Serotonin and melatonin synthesis](https://durgical.com/en/biochemistry/pathways/serotonin-and-melatonin-synthesis/) - [Adrenaline](https://durgical.com/en/biochemistry/molecules/adrenaline/) - [Catecholamines: synthesis and breakdown](https://durgical.com/en/biochemistry/topics/catecholamines-synthesis-and-breakdown/) ## Test yourself Think of the answer, then tap the question to see it. ## Which step limits the rate of catecholamine synthesis? Tyrosine hydroxylase, which needs BH4, Fe²⁺ and O₂ and is inhibited by dopamine and norepinephrine. ## Why is levodopa given with carbidopa? Carbidopa blocks DOPA decarboxylase outside the brain, so more levodopa reaches the brain and fewer peripheral effects of dopamine appear. ## Why is epinephrine made almost only in the adrenal medulla? PNMT is induced by the high cortisol that reaches the medulla from the cortex through the adrenal portal circulation. ## Which test screens for phaeochromocytoma, and why? Plasma free or urine fractionated metanephrines: COMT inside the tumour makes them continuously, so they are high even between attacks. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/catecholamine-synthesis-and-breakdown/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [TH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/th/) (MedlinePlus, US National Library of Medicine, 2026); [Aromatic l-amino acid decarboxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [Dopamine beta-hydroxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/dopamine-beta-hydroxylase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [Phenylethanolamine N-methyltransferase (PNMT) - Homo sapiens](https://www.uniprot.org/uniprotkb/P11086/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. 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