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

Dopa decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase (AADC), is a pyridoxal 5-phosphate-dependent enzyme that plays a vital role in the biosynthesis of the neurotransmitters dopamine and serotonin [1, 2]. It catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and 5-hydroxytryptophan (5-HTP) to serotonin [1]. In the striatum, DDC activity is essential for motor function, but it is severely diminished in Parkinson's disease due to the progressive loss of dopaminergic neurons [4]. To address this, gene therapy approaches utilize viral vectors to deliver the DDC gene directly into striatal neurons, enabling them to convert exogenous L-DOPA into dopamine independently of the lost nigrostriatal projections [3, 4]. Additionally, peripheral DDC inhibitors like carbidopa are standard co-treatments with L-DOPA to prevent systemic metabolism and increase central nervous system bioavailability [2]. Mutations in the DDC gene also lead to AADC deficiency, a rare and debilitating genetic disorder characterized by severe motor and autonomic dysfunction [3].

Other names

Aromatic L-amino acid decarboxylaseAADCDOPA decarboxylaseTryptophan decarboxylase5-hydroxytryptophan decarboxylase

DDC catalyzes the decarboxylation of L-DOPA to dopamine and 5-HTP to serotonin. In Parkinson's disease, peripheral inhibitors (e.g., carbidopa) are used to prevent the systemic conversion of L-DOPA, while gene therapy (e.g., eladocagene exuparvovec) delivers the DDC gene to striatal neurons to restore local dopamine synthesis from L-DOPA [2, 3, 4].