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

Aromatic L-amino acid decarboxylase (AADC), encoded by the DDC gene, is a pyridoxal phosphate-dependent enzyme responsible for the final step in the synthesis of the key neurotransmitters dopamine and serotonin (UniProt P20711). It catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and L-5-hydroxytryptophan to serotonin (NCBI Gene 1644). In the context of Parkinson's disease, peripheral AADC is inhibited by drugs like carbidopa to prevent the premature conversion of exogenous L-DOPA, thereby increasing its transport across the blood-brain barrier (StatPearls). Conversely, AADC deficiency is a rare autosomal recessive genetic disorder characterized by a lack of this enzyme, leading to severe developmental delays and motor dysfunction (NIH GARD). Recent therapeutic advances include gene therapy, such as eladocagene exuparvovec, designed to deliver a functional DDC gene directly into the brain to restore neurotransmitter production (EMA). The enzyme also plays a role in the synthesis of other trace amines like tryptamine and phenylethylamine (PubChem). Monitoring of AADC function often involves measuring metabolite levels in cerebrospinal fluid or plasma, such as 3-O-methyldopa (PubMed PMID: 33530101).

Other names

DOPA decarboxylaseDDCAromatic L-amino-acid decarboxylaseTryptophan decarboxylase

Inhibition of peripheral decarboxylation of L-DOPA to increase central nervous system availability; gene replacement therapy to restore enzymatic activity in deficient patients.