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What is the role of ascorbic acid in norepinephrine synthesis and orthostatic hypotension?

Ascorbic acid (ascorbate) participates in critical steps of the biosynthesis of norepinephrine, including those mediated by tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH). For example, DBH is responsible for the conversion of dopamine into norepinephrine in noradrenergic terminals and requires the activity of the ascorbate-coupled cytochrome b561 protein (CYB561). The recent identification of 2 families harboring CYB561 gene mutations manifested with longstanding orthostatic hypotension (OH)1,2 resembling the phenotype of DBH deficiency3,4 emphasizes the important role of ascorbic acid–related processes in sympathetic control of blood pressure.