phenylethanolamineNmethyltransferase

Phenylethanolamine N-methyltransferase (PNMT) is a cytosolic enzyme that catalyzes the methylation of norepinephrine to epinephrine, using S-adenosyl-L-methionine (SAM) as the methyl donor and producing S-adenosyl-L-homocysteine (SAH) as a byproduct. It represents the final step in the biosynthesis of epinephrine in the catecholamine pathway.

Distribution and function: PNMT is predominantly expressed in the adrenal medulla chromaffin cells, where epinephrine is released into the bloodstream. It is also present at lower levels in certain brain regions and other tissues. By converting norepinephrine to epinephrine, PNMT helps determine the epinephrine-to-norepinephrine ratio, influencing the hormonal and nervous system responses to stress, including cardiovascular and metabolic effects.

Regulation: Expression of PNMT is strongly upregulated by glucocorticoids, particularly cortisol, through glucocorticoid receptor–mediated activation of the PNMT gene promoter. This regulatory link connects stress hormone signaling to the synthesis of epinephrine. Neural activity and developmental or physiological factors can also modulate PNMT levels.

Gene and structure: In humans, PNMT is encoded by the PNMT gene. The enzyme belongs to the family of methyltransferases and operates in the cytosol of adrenergic cells.

Clinical relevance: Variations in PNMT activity can affect the balance of epinephrine and norepinephrine, with potential implications for stress physiology and cardiovascular function. PNMT deficiency is rare, and most clinical interest centers on its role in regulating the adrenal epinephrine response.

See also: Catecholamine biosynthesis, Epinephrine, Norepinephrine, Adrenal medulla.