Catecholamine Synthesis

1. 1

   L-Tyrosine + O2 + BH4 -> L-DOPA + BH2 + H2O

   Tyrosine hydroxylase (TH) 1.14.16.2 ST-0341 Irreversible rate-limiting BH4 O2 Fe2+
   In Tyrosine O2 BH4

   Out L-DOPA BH2 H2O
   › Notes

   Rate-limiting step of catecholamine synthesis; feedback-inhibited by the end-product catecholamines.

2. 2

   L-DOPA -> dopamine + CO2

   Aromatic L-amino acid decarboxylase (DDC) 4.1.1.28 ST-0342 Irreversible/directional PLP (B6)
   In L-DOPA

   Out Dopamine CO2
   › Notes

   Peripheral inhibition of DDC by carbidopa is what allows levodopa to reach the brain.

3. 3

   Dopamine + O2 + ascorbate -> norepinephrine

   Dopamine beta-hydroxylase (DBH) 1.14.17.1 ST-0343 Irreversible/directional Ascorbate (vit C) Cu
   In Dopamine O2 Ascorbate

   Out Norepinephrine
   › Notes

   Occurs inside the storage vesicle; copper- and vitamin C-dependent.

4. 4

   Norepinephrine + SAM -> epinephrine + SAH

   Phenylethanolamine N-methyltransferase (PNMT) 2.1.1.28 ST-0344 Irreversible/directional SAM
   In Norepinephrine S-adenosylmethionine (SAM)

   Out Epinephrine S-adenosylhomocysteine
   › Notes

   Confined largely to adrenal medulla, where cortisol from the cortex induces PNMT.

5. 5

   Catecholamines -> metanephrines/normetanephrine -> vanillylmandelic acid (VMA)

   Catechol-O-methyltransferase (COMT) + monoamine oxidase (MAO) 2.1.1.6 / 1.4.3.4 ST-0345 Irreversible/directional SAM FAD
   In Catecholamines

   Out Metanephrines/normetanephrine
   › Notes

   Urinary metanephrines and VMA are the screening metabolites for phaeochromocytoma; dopamine degrades to homovanillic acid.

Showing all 5 steps.