Dopa Decarboxylase Human
Description
Overview of Dopa Decarboxylase (DDC) in Humans
Dopa decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase (AADC), is a pyridoxal 5′-phosphate (PLP)-dependent enzyme encoded by the DDC gene on human chromosome 7 (7p12.2-p12.1) . It catalyzes the decarboxylation of aromatic amino acids, including L-DOPA and 5-hydroxytryptophan (5-HTP), to produce dopamine and serotonin, respectively . These neurotransmitters are critical for motor coordination, mood regulation, and autonomic functions. DDC also synthesizes trace amines like phenethylamine and tyramine, which modulate neuronal activity .
Key Biochemical Properties
Regulatory Mechanisms
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Phosphorylation: Protein kinase A (PKA) and protein kinase G (PKG) phosphorylate DDC at residues S220, S336, and S359, enhancing its activity .
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Dopamine Receptor Feedback: Dopamine receptor antagonists increase DDC activity, while agonists like apomorphine suppress it .
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Oxidative Stress: DDC expression remains stable or increases under oxidative conditions, suggesting a protective role in neural cells .
Genetic Mutations and AADC Deficiency
Over 60 pathogenic variants in the DDC gene cause aromatic L-amino acid decarboxylase deficiency (AADCD), an autosomal recessive disorder characterized by severe developmental delays, oculogyric crises, and autonomic dysfunction . These mutations reduce enzyme activity by 60–95%, leading to dopamine and serotonin depletion .
Clinical Management of AADCD
Role in Parkinsonian Disorders
DDC is a biomarker candidate for Lewy body diseases (LBD) and atypical Parkinsonian disorders. Cerebrospinal fluid (CSF) DDC levels distinguish LBD patients from controls with 89% accuracy (AUC = 0.89) and predict progression to clinical LBD in preclinical cases (hazard ratio = 3.7) . Plasma DDC levels correlate with dopaminergic therapy, reflecting compensatory upregulation in response to neurodegeneration .
Diagnostic Utility of DDC in Parkinsonian Disorders
| Biomarker Source | Cohort Findings |
|---|---|
| CSF | Elevated in LBD and atypical Parkinsonism; predicts cognitive decline |
| Plasma | Increased in treated Parkinson’s disease patients (AUC = 0.71) |
Pharmacological Relevance
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Levodopa Therapy: DDC converts oral L-DOPA to dopamine in Parkinson’s disease. Co-administration with carbidopa (a peripheral DDC inhibitor) enhances central efficacy .
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Drug Interactions: Flupenthixol (a dopamine antagonist) increases cerebral DDC activity by 50%, while apomorphine reduces it by 20% .
Emerging Research Directions
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Biomarker Validation: Ongoing studies aim to standardize DDC measurements in CSF and plasma for early LBD detection .
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Oxidative Stress Response: DDC overexpression mitigates H₂O₂-induced cytotoxicity, implicating it in neuroprotective pathways .
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Structural Studies: Crystal structures of DDC-carbidopa complexes inform drug design for Parkinson’s disease .
Product Specs
Dopa decarboxylase, a key enzyme in neurotransmitter synthesis, is a homodimeric enzyme that depends on pyridoxal phosphate for its activity. This enzyme plays a crucial role in two metabolic pathways responsible for producing two important neurotransmitters implicated in various clinical conditions, including Parkinson's disease. Primarily located in the basal ganglia of the brain, dopa decarboxylase catalyzes the conversion of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin, and L-tryptophan to tryptamine. Deficiencies in dopa decarboxylase can lead to aromatic L-amino-acid decarboxylase deficiency (AADCD), an inherited metabolic disorder characterized by a combined deficiency of serotonin and catecholamine neurotransmitters.
Product Science Overview
DDC is a 54 kDa enzyme that catalyzes the decarboxylation of aromatic L-amino acids to produce the corresponding amines . Specifically, it converts:
- L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine
- L-5-hydroxytryptophan to serotonin
These neurotransmitters, dopamine and serotonin, play significant roles in the central nervous system and are involved in various physiological processes .
The enzyme’s activity is of particular interest in medical research due to its involvement in the synthesis of neurotransmittersL-DOPA is commonly used to treat the symptoms of Parkinson’s disease, a neurodegenerative disorder characterized by dopamine deficiency . Additionally, DDC’s role in serotonin production links it to mood regulation and conditions such as schizophrenia and depression .
Recombinant human Dopa Decarboxylase is produced using various expression systems, such as baculovirus-insect cells . This recombinant form is used in research to study the enzyme’s properties and its potential therapeutic applications. The recombinant enzyme is typically purified to high levels of purity (>90%) and is tested for its bioactivity, ensuring it can effectively convert L-DOPA to dopamine .
Research on DDC includes studying its structure, function, and potential inhibitors. Inhibiting DDC can be a strategy for treating conditions like schizophrenia and Parkinson’s disease . The enzyme’s activity is measured by its ability to convert substrates like L-DOPA to dopamine, with specific activity levels indicating its efficiency .
