dopadescarboxilase

Dopa decarboxylase, also known as L-DOPA decarboxylase or aromatic L-amino acid decarboxylase (AADC), is a pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-DOPA to dopamine. It also decarboxylates 5-hydroxytryptophan to serotonin and participates in the biosynthesis of other monoamines in various tissues.

In humans, the enzyme is encoded by the DDC gene and is expressed in dopaminergic and noradrenergic neurons of the central nervous system as well as in peripheral tissues such as enterochromaffin cells of the gut. The protein is typically a cytosolic homodimer that binds PLP as a cofactor. The catalytic mechanism involves formation of a Schiff base between PLP and an active-site lysine, followed by decarboxylation and release of the amine product.

Physiologically, AADC is essential for the production of dopamine and serotonin, influencing motor control, mood, and autonomic function. Its activity can be influenced by vitamin B6 status, and pharmacologically by inhibitors such as carbidopa, which restricts peripheral conversion of L-DOPA and improves central availability in the treatment of Parkinson's disease.

Clinically, deficiency of aromatic L-amino acid decarboxylase (AADC deficiency) is a rare genetic disorder characterized by deficits in central monoamine neurotransmitters, leading to movement disorders and autonomic dysfunction. Treatment strategies include L-DOPA with carbidopa and other dopaminergic or serotonergic agents, sometimes with pyridoxine supplementation.

Beyond physiology and medicine, DDC and AADC are used in research and clinical contexts for the enzymatic synthesis of monoamines and in assays of PLP-dependent decarboxylases.