8th Endocrine Lecture: Hormone Synthesis

Decarboxylation

• Decarboxylation occurs in secretion granules of chromaffin cells.
• It involves the side chain hydroxylation of dopamine, resulting in the formation of norepinephrine.
• The reaction is catalyzed by dopamine β-hydroxylase (DBH) enzyme in the presence of ascorbate, copper, and fumarate as coenzymes.
• This reaction is irreversible.
• Once norepinephrine is formed, it returns to the cytoplasm for further steps.

Side Chain Hydroxylation

• No additional information provided.

N-Methylation

• N-methylation occurs in the cytoplasm of chromaffin cells.
• It involves the N-methylation of norepinephrine, resulting in the formation of epinephrine.
• The reaction is catalyzed by phenylethanolamine-N-methyltransferase (PNMT) enzyme.
• The synthesis of PNMT requires an induction process by high glucocorticoid hormones concentration (100-fold concentration gradient over systemic blood).
• This high glucocorticoid concentration is present in the adrenal medulla, explaining why epinephrine is the main product of adrenal medulla.
• In contrast, norepinephrine is the main product of extramedullary tissues due to the lack of high glucocorticoid concentration.

Storage and Release of Hormones

• After formation, dopamine, norepinephrine, and epinephrine are stored in secretion granules of chromaffin cells.
• They are released on demand.