dopaminehydroxylase

Dopamine beta-hydroxylase (DBH) is a copper-dependent monooxygenase that catalyzes the conversion of dopamine to norepinephrine in the catecholamine biosynthesis pathway. The enzymatic reaction uses molecular oxygen and ascorbate as cofactors, producing norepinephrine, water, and dehydroascorbate.

DBH is primarily localized in the secretory vesicles of postganglionic sympathetic neurons and adrenal chromaffin cells, where it is stored with norepinephrine and released together during exocytosis. Copper is the essential metal cofactor in its active site, and ascorbate maintains the enzyme in a reduced state during turnover.

The enzyme is encoded by the DBH gene. Variation in DBH activity across individuals influences plasma levels of norepinephrine and related autonomic functions. A rare genetic disorder called dopamine beta-hydroxylase deficiency results from DBH mutations and is characterized by low norepinephrine and epinephrine, elevated dopamine, and autonomic dysfunction such as orthostatic hypotension.

Clinical relevance includes the measurement of plasma DBH activity as a biomarker of sympathetic nervous system activity in research and certain clinical assessments. Therapeutically, individuals with DBH deficiency can be treated with L-threo-3,4-dihydroxyphenylserine (L-DOPS), a precursor that bypasses the enzymatic block by providing a norepinephrine precursor that is converted downstream to norepinephrine.