USMLE Step 1


Biochemical Pathways

Catecholamine Synthesis & Breakdown
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Catecholamine Synthesis Mnemonic

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Catecholamine Synthesis is a biochemical pathway used to produce dopamine, norepinephrine, and epinephrine. This process takes place in the adrenal medulla as well as the post-ganglionic fibers of the sympathetic nervous system.

The pathway begins with phenylalanine, which is converted into tyrosine. This reaction is catalyzed by the enzyme phenylalanine hydroxylase, and requires the cofactor, BH4 (tetrahydrobiopterin) . Notably, this reaction is impaired in patients with Phenylketonuria.

Next, tyrosine is converted into DOPA, by the enzyme tyrosine hydroxylase. Tyrosine hydroxylase also requires a BH4 cofactor. Afterwards, DOPA is converted into dopamine, by the enzyme DOPA decarboxylase. This reaction requires Vitamin B6 (Pyridoxine) as a cofactor, and can be blocked by the drug, carbidopa.

Subsequently, dopamine is converted into norepinephrine. This reaction is catalyzed by dopamine beta-hydroxylase, and requires Vitamin C (Ascorbic Acid) as a cofactor. Finally, norepinephrine is methylated by PNMT, producing epinephrine. This reaction requires SAM as a cofactor, and can be stimulated by cortisol.

Catecholamine Breakdown is a separate biochemical pathway used to metabolize and eliminate catecholamines. Dopamine is degraded into homovanillic acid, while norepinephrine and epinephrine are first converted into metanephrines by the enzyme COMT. These metanephrines are then further degraded into vanillylmandelic acid, a reaction catalyzed by the MAO enzymes.

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