Catecholamine Synthesis & Breakdown
Catecholamine synthesis begins with phenylalanine, which is converted into tyrosine. This reaction is catalyzed by the enzyme phenylalanine hydroxylase, and requires the cofactor BH4. 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 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 as a cofactor. Finally, Norepinephrine is methylated by PNMT, becoming Epinephrine. This reaction requires SAM to be present as a cofactor, and can be stimulated by cortisol. Catecholamine breakdown involves a different set of enzymes and products. Dopamine is degraded into homovanillic acid. On the other hand, norepinephrine and epinephrine are first converted into metanephrines by the enzyme COMT. These metanephrines are then further degraded into Vanillylmandelic acid.