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

Aromatic L-amino acid decarboxylase (AADC), encoded by the DDC gene, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and 5-hydroxytryptophan (5-HTP) to serotonin (UniProt P20711). In clinical practice, the peripheral expression of AADC is a major target for the treatment of Parkinson's disease to prevent the systemic metabolism of exogenous levodopa (StatPearls, Levodopa). Peripheral AADC inhibitors like carbidopa and benserazide are co-administered with levodopa because they cannot cross the blood-brain barrier; this ensures that levodopa remains intact until it reaches the central nervous system (PubChem, CID 4672). This targeted inhibition increases the half-life of levodopa in the plasma and reduces the incidence of peripheral side effects such as nausea and tachycardia caused by high levels of circulating dopamine (PubMed, PMID 25663150). Beyond its role in Parkinson's, AADC is essential for the synthesis of trace amines like tryptamine and tyramine, and its genetic deficiency leads to a rare, severe neurometabolic disorder (NIH, GARD). The enzyme is also involved in the production of histamine in certain tissues, further highlighting its broad metabolic significance. Pharmacological modulation of peripheral AADC remains a cornerstone of dopaminergic therapy, allowing for lower doses of levodopa and improved patient outcomes.

Other names

DOPA decarboxylaseDDC5-hydroxytryptophan decarboxylaseTryptophan decarboxylaseAromatic L-amino acid decarboxylase, peripheralAromatic L-amino acid decarboxylase (peripheral)

Peripheral inhibition of the decarboxylation of L-DOPA to dopamine, increasing central bioavailability of levodopa and reducing systemic side effects.