Catecholamine biosynthesis pathway Overview
The catecholamine biosynthesis pathway, also known as the catecholamine synthesis or metabolic pathway, is a series of enzymatic reactions responsible for producing key neurotransmitters and hormones—dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline)—from dietary amino acids. The process begins with phenylalanine being converted into tyrosine by phenylalanine hydroxylase. Tyrosine is then converted into L-DOPA by tyrosine hydroxylase—the rate-limiting step—followed by decarboxylation via aromatic L-amino acid decarboxylase to form dopamine. Dopamine can be further converted into norepinephrine by dopamine β-hydroxylase; finally, norepinephrine may be methylated by phenylethanolamine N-methyltransferase primarily in adrenal medullary cells to produce epinephrine[1][3][4][5]. This biochemical sequence occurs mainly in neurons and chromaffin cells. Dysregulation at any step can contribute to various diseases including neurodegenerative disorders like Parkinson's disease, endocrine tumors such as pheochromocytoma that overproduce catecholamines[2], cardiovascular conditions like hypertension[7], and psychiatric illnesses.
Mechanism of Action
Inhibition of tyrosine hydroxylase to reduce catecholamine synthesis. Inhibition of vesicular monoamine transporter to deplete neurotransmitter stores. Precursor supplementation to increase neurotransmitter levels.
Biological Functions
Disease Associations
Safety Considerations
- Risk of severe hypotension or hypertensive crisis when altering catecholamine production/release
- Psychiatric side effects from depletion therapies
- Motor dysfunction with excessive inhibition in Parkinson’s treatment context
Interacting Drugs
Associated Biomarkers
Biomarker |
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Plasma/urinary metanephrines and normetanephrines for pheochromocytoma diagnosis |
Dopamine, norepinephrine, epinephrine levels in plasma/CSF |