Aromatic L-amino acid decarboxylase (DDC) (AADC)

Aromatic L-amino acid decarboxylase (AADC), encoded by the DDC gene, is a pyridoxal phosphate-dependent enzyme that catalyzes the final step in the biosynthesis of the neurotransmitters dopamine and serotonin [1]. It functions by removing a carboxyl group from L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP), making it essential for motor control, mood regulation, and autonomic function [2]. In the clinical management of Parkinson's disease, AADC is the primary enzyme responsible for converting the therapeutic prodrug levodopa into active dopamine within the brain [4]. However, because AADC is also widely expressed in peripheral tissues, it can prematurely convert levodopa into dopamine before it crosses the blood-brain barrier, leading to systemic side effects such as nausea and hypotension [2]. To mitigate this, AADC inhibitors like carbidopa are co-administered to block peripheral conversion while sparing central enzyme activity [4]. Beyond Parkinson's, genetic mutations in the DDC gene cause AADC deficiency, a severe neurometabolic disorder that results in global developmental delay and oculogyric crises [3]. Recent therapeutic advances include gene therapy (e.g., eladocagene exuparvovec) designed to deliver a functional DDC gene to the brain to restore neurotransmitter production in deficient patients [3].

Other names

DOPA decarboxylaseDDCTryptophan decarboxylase5-hydroxytryptophan decarboxylaseAromatic L-amino-acid decarboxylase

AADC catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and 5-hydroxytryptophan (5-HTP) to serotonin [1]. In Parkinson's therapy, peripheral AADC inhibitors like carbidopa are used to prevent the systemic conversion of L-DOPA, ensuring more of the prodrug reaches the central nervous system for conversion by brain AADC [2, 4].