DBH

Dopamine beta-hydroxylase (DBH) is an enzyme that catalyzes the conversion of dopamine to norepinephrine, a key step in the biosynthesis of catecholamines in noradrenergic neurons and the adrenal medulla. It is a copper-dependent monooxygenase that operates in secretory vesicles, where it acts on dopamine prior to neurotransmitter release. The activity of DBH links cerebral and peripheral catecholamine pools and influences sympathetic tone and stress responses.

The DBH gene encodes the enzyme, and its expression is prominent in brain regions with dense noradrenergic innervation as well as in sympathetic neurons. The enzyme relies on cofactors such as copper and ascorbate for catalytic activity, and its function can be modulated by genetic variation and physiological state.

Clinical significance of DBH includes the existence of rare DBH deficiency, an autosomal recessive disorder characterized by markedly reduced norepinephrine and epinephrine synthesis. Patients may present with orthostatic hypotension, ptosis, nasal congestion, and impaired stress responsiveness. Diagnosis often involves measuring plasma or cerebrospinal fluid DBH activity and catecholamine levels. Treatment options include the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa) to bypass the enzymatic step and increase norepinephrine availability.

In research and clinical practice, plasma DBH activity serves as a biomarker of sympathetic nervous system activity. Genetic variants in DBH and corresponding enzyme activity have been studied in relation to psychiatric traits and treatment responses. Animal models lacking DBH help researchers understand the role of noradrenergic signaling in stress, arousal, and mood regulation.