Structure and synthesis of endogenous catecholamines


tyrosine molecule

Tyrosine  is a boring non-essential amino acid. Soft cheese (tyros) serves as a delicious source of it. Additionally you can synthesise it out of phenylalanine.

L-Dopa (Levo-DihydrOxyPhenylAlanine)

L-DOPA molecule

L-Dopa  is tyrosine plus an extra hydroxyl group. It crosses the blood brain barrier and acts as a precursor for dopamine.


dopamine molecule

Dopamine is the prototype catecholamine. It is naked and undecorated, a pure catechol ring attached to a pure ethylamine string.  There are no additional groups to confuse its simple elegance. It lacks a beta-carbon group, so it is a weak agonist of both beta and alpha. As it has both catechol hydroxyl groups and no alpha-carbon group, it is a substrate for both MAO and COMT.


noradrenaline molecule

Noradrenaline is the prototypical alpha-agonist.

The hydroxyl group on its beta-carbon increases its potency, and the absence of alkyl substitutes on the amine group gives it a degree of alpha-1 selectivity, but takes away beta-activity.


Adrenaline molecule

Adrenaline is the prototypical mixed agonist.
The additional methyl group greatly increases both alpha-activity (even more than noradrenaline) and beta-activity.
The full complement of hydroxyl groups on the catechol ring and beta-carbon maximize receptor affinity.
Adrenaline is the thus most potent and least selective sympathomimetic.

Synthesis pathways of endogenous catecholamines

synthesis of endogenous catecholamines

First, you 3-hydroxylate tyrosine to  yield L-dopa.

This first step is the rate-limiting step of catecholamine synthesis.

It happens in the cytoplasm of the body of the neuron.

When the adrenal medulla is stimulated, this tyrosine hydroxylase  is the enzyme that gets phosphorylated by protein kinase C and calmodulin. Thus, to get systemic release of adrenaline in a fight-or-flight situation, tyrosine must be hydroxylated at a sufficient rate.

Then, you decarboxylate your L-dopa with a pinch of pyridoxine, which results in dopamine. This also happens in the neuronal body cytoplasm. The resulting dopamine is then sucked up into storage vesicles.


The vesicles are then slowly transported towards the synapses by axoplasmic flow.

The dopamine is beta-hydroxylated to form noradrenaline inside the storage vesicles. The noradrenaline then sits and waits patiently to be released into the synaptic cleft.

Not only is noradrenaline synthesised de-novo, it is also replenished by reuptake from the synaptic cleft.

Noradrenaline is N-methylated to form adrenaline in the chromaffin cells of the adrenal medulla. This doesn’t happen in the vesicles – noradrenaline has to leave the vesicles to be converted into adrenaline; and then it is taken up into another bunch of different vesicles.

Weirdly, the size of the adrenaline store is controlled by glucocorticoids. Glucocorticoids travel via the intra-adrenal portal venous network into the medulla, to induce the synthesis of phenethanolamine N-methyltransferase.


For this sort of really basic stuff, no matter where you look you will find essentially the same information.

I used chapters from "Goodman & Gilman's The Pharmacological Basis of Therapeutics" 11th ed by Brunton et al, and "Basic & Clinical Pharmacology" 11th ed. By Katzung et al.

I also perused Peck and Hill "Pharmacology for Anaesthesia and Intensive care" as well as the notoriously error-prone "Handbook of Pharmacology and Physiology in Anaesthetic Practice" by Stoelting and Hillier. Neither covered this subject in a depth I found satisfying.

Goodman and Gilman's remains a canonical text.