Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DETK9CN)

DME Name DOPA decarboxylase (DDC)
Synonyms Aromatic-L-amino-acid decarboxylase; Tryptophan decarboxylase; 5-hydroxytryptophan decarboxylase; AADC; DDC
Gene Name DDC
UniProt ID
DDC_HUMAN
INTEDE ID
DME0125
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
1644
EC Number EC: 4.1.1.28
Lyases
Carbon-carbon lyase
Carboxy-lyase
EC: 4.1.1.28
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MNASEFRRRGKEMVDYMANYMEGIEGRQVYPDVEPGYLRPLIPAAAPQEPDTFEDIINDV
EKIIMPGVTHWHSPYFFAYFPTASSYPAMLADMLCGAIGCIGFSWAASPACTELETVMMD
WLGKMLELPKAFLNEKAGEGGGVIQGSASEATLVALLAARTKVIHRLQAASPELTQAAIM
EKLVAYSSDQAHSSVERAGLIGGVKLKAIPSDGNFAMRASALQEALERDKAAGLIPFFMV
ATLGTTTCCSFDNLLEVGPICNKEDIWLHVDAAYAGSAFICPEFRHLLNGVEFADSFNFN
PHKWLLVNFDCSAMWVKKRTDLTGAFRLDPTYLKHSHQDSGLITDYRHWQIPLGRRFRSL
KMWFVFRMYGVKGLQAYIRKHVQLSHEFESLVRQDPRFEICVEVILGLVCFRLKGSNKVN
EALLQRINSAKKIHLVPCHLRDKFVLRFAICSRTVESAHVQRAWEHIKELAADVLRAERE
Function This enzyme catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
KEGG Pathway
Alcoholism (hsa05034 )
Amphetamine addiction (hsa05031 )
Cocaine addiction (hsa05030 )
Dopaminergic synapse (hsa04728 )
Metabolic pathways (hsa01100 )
Phenylalanine metabolism (hsa00360 )
Serotonergic synapse (hsa04726 )
Tryptophan metabolism (hsa00380 )
Tyrosine metabolism (hsa00350 )
Reactome Pathway
Serotonin and melatonin biosynthesis (R-HSA-209931 )
Catecholamine biosynthesis (R-HSA-209905 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
3 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Droxidopa DM5YF4M Chronic fatigue syndrome 8E49 Approved [13]
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [14]
Levodopa DMN3E57 Parkinson disease 8A00.0 Approved [15]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 1.16E-01 -4.27E-02 -2.29E-01
Alopecia ED70 Skin from scalp 1.85E-01 4.68E-02 1.39E-01
Alzheimer's disease 8A20 Entorhinal cortex 1.35E-03 -7.92E-02 -4.01E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 2.93E-01 -1.05E-01 -1.42E+00
Aortic stenosis BB70 Calcified aortic valve 7.32E-01 3.99E-03 1.05E-02
Apnea 7A40 Hyperplastic tonsil 2.14E-01 2.81E-02 1.27E-01
Arthropathy FA00-FA5Z Peripheral blood 1.71E-01 -5.22E-02 -5.60E-01
Asthma CA23 Nasal and bronchial airway 4.90E-08 -2.12E-01 -5.97E-01
Atopic dermatitis EA80 Skin 1.98E-01 -5.79E-02 -3.94E-01
Autism 6A02 Whole blood 4.60E-01 -3.67E-02 -2.29E-01
Autoimmune uveitis 9A96 Peripheral monocyte 3.43E-03 -2.41E-01 -2.31E+00
Autosomal dominant monocytopenia 4B04 Whole blood 6.52E-01 5.14E-02 4.30E-01
Bacterial infection of gingival 1C1H Gingival tissue 4.93E-01 -5.07E-02 -2.61E-01
Batten disease 5C56.1 Whole blood 3.55E-01 4.87E-03 1.28E-01
Behcet's disease 4A62 Peripheral blood 2.92E-01 1.45E-01 9.21E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 1.89E-01 -7.97E-02 -2.88E-01
Bladder cancer 2C94 Bladder tissue 1.85E-02 6.82E-01 1.57E+00
Breast cancer 2C60-2C6Z Breast tissue 2.61E-01 -1.30E-01 -3.11E-01
Cardioembolic stroke 8B11.20 Whole blood 9.32E-01 7.04E-03 6.28E-02
Cervical cancer 2C77 Cervical tissue 6.75E-01 3.92E-02 2.27E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 8.83E-01 -1.89E-03 -7.46E-03
Chronic hepatitis C 1E51.1 Whole blood 6.45E-02 9.27E-02 1.27E+00
Chronic obstructive pulmonary disease CA22 Lung tissue 1.00E-01 7.15E-03 2.85E-02
Chronic obstructive pulmonary disease CA22 Small airway epithelium 9.54E-03 9.03E-02 3.54E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 4.01E-01 -4.72E-02 -9.18E-01
Colon cancer 2B90 Colon tissue 1.66E-49 -7.88E-01 -1.55E+00
Coronary artery disease BA80-BA8Z Peripheral blood 7.17E-01 -3.59E-02 -3.26E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 8.43E-01 1.99E-03 1.41E-02
Endometriosis GA10 Endometrium tissue 2.85E-01 2.06E-02 1.38E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 5.27E-01 8.71E-03 7.90E-02
Familial hypercholesterolemia 5C80.00 Whole blood 1.59E-04 -1.75E-01 -7.29E-01
Gastric cancer 2B72 Gastric tissue 3.80E-02 2.05E+00 3.32E+00
Glioblastopma 2A00.00 Nervous tissue 6.85E-01 4.07E-02 7.09E-02
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 4.41E-03 -1.78E-01 -1.75E+01
Glioma 2A00.0Y-2A00.0Z White matter tissue 7.12E-04 -4.91E-01 -1.87E+00
Head and neck cancer 2D42 Head and neck tissue 2.99E-12 -2.21E-01 -8.61E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 4.04E-01 -3.87E-02 -2.25E-01
Huntington's disease 8A01.10 Whole blood 9.17E-01 -3.25E-02 -3.19E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 2.85E-01 1.28E-01 5.13E-01
Immunodeficiency 4A00-4A20 Peripheral blood 1.10E-01 2.38E-02 2.74E-01
Influenza 1E30 Whole blood 4.58E-01 -3.38E-02 -3.15E-01
Interstitial cystitis GC00.3 Bladder tissue 4.31E-01 -1.82E-02 -5.48E-02
Intracranial aneurysm 8B01.0 Intracranial artery 7.50E-01 -7.67E-03 -6.86E-02
Irritable bowel syndrome DD91.0 Rectal colon tissue 6.67E-03 -2.23E-01 -6.27E-01
Ischemic stroke 8B11 Peripheral blood 2.70E-01 9.14E-02 1.03E+00
Juvenile idiopathic arthritis FA24 Peripheral blood 4.73E-03 7.10E-02 3.92E-01
Lateral sclerosis 8B60.4 Skin 4.20E-01 6.51E-02 4.07E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 4.26E-02 1.53E-01 1.11E+00
Liver cancer 2C12.0 Liver tissue 1.16E-03 -3.64E-01 -4.92E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.37E-02 -1.20E+00 -7.77E+00
Lung cancer 2C25 Lung tissue 9.67E-01 -5.42E-01 -1.21E+00
Lupus erythematosus 4A40 Whole blood 2.32E-01 -6.68E-02 -2.38E-01
Major depressive disorder 6A70-6A7Z Hippocampus 4.40E-01 -1.41E-02 -5.11E-02
Major depressive disorder 6A70-6A7Z Whole blood 4.80E-01 3.68E-02 1.72E-01
Melanoma 2C30 Skin 4.32E-04 -3.64E-01 -6.05E-01
Multiple myeloma 2A83.1 Peripheral blood 8.05E-01 2.31E-02 1.29E-01
Multiple myeloma 2A83.1 Bone marrow 1.14E-02 -1.51E-01 -1.08E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 9.35E-01 6.57E-02 3.69E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 8.55E-01 1.45E-02 1.17E-01
Myelofibrosis 2A20.2 Whole blood 3.04E-01 3.81E-02 3.86E-01
Myocardial infarction BA41-BA50 Peripheral blood 3.06E-02 1.35E-01 5.30E-01
Myopathy 8C70.6 Muscle tissue 3.03E-02 -1.88E-01 -8.16E-01
Neonatal sepsis KA60 Whole blood 5.05E-02 -5.50E-02 -2.56E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 3.39E-03 1.42E-01 5.68E-01
Non-alcoholic fatty liver disease DB92 Liver tissue 1.86E-01 1.94E-01 4.88E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 3.96E-01 8.43E-02 6.41E-01
Olive pollen allergy CA08.00 Peripheral blood 7.80E-02 2.12E-01 1.45E+00
Oral cancer 2B6E Oral tissue 4.19E-06 -2.52E-01 -1.27E+00
Osteoarthritis FA00-FA0Z Synovial tissue 4.47E-02 -1.39E-01 -5.89E-01
Osteoporosis FB83.1 Bone marrow 1.95E-01 9.72E-02 2.59E+00
Ovarian cancer 2C73 Ovarian tissue 1.96E-01 -1.08E-01 -5.10E-01
Pancreatic cancer 2C10 Pancreas 4.00E-01 3.85E-02 6.55E-02
Parkinson's disease 8A00.0 Substantia nigra tissue 7.84E-03 -1.49E+00 -1.01E+00
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 8.56E-01 -1.68E-02 -1.54E-01
Pituitary cancer 2D12 Pituitary tissue 2.52E-03 2.83E-01 2.70E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 4.56E-01 4.79E-02 4.07E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 2.78E-01 5.78E-02 3.01E-01
Polycythemia vera 2A20.4 Whole blood 6.46E-02 6.32E-02 5.84E-01
Pompe disease 5C51.3 Biceps muscle 4.54E-04 -3.71E-01 -2.10E+00
Preterm birth KA21.4Z Myometrium 4.45E-01 -7.15E-02 -4.63E-01
Prostate cancer 2C82 Prostate 3.69E-03 1.89E-01 4.15E-01
Psoriasis EA90 Skin 3.65E-03 -1.23E-01 -2.89E-01
Rectal cancer 2B92 Rectal colon tissue 1.48E-05 -7.64E-01 -3.46E+00
Renal cancer 2C90-2C91 Kidney 3.16E-03 -2.81E+00 -1.86E+00
Retinoblastoma 2D02.2 Uvea 4.37E-11 -4.17E+00 -1.84E+01
Rheumatoid arthritis FA20 Synovial tissue 9.77E-02 -1.72E-01 -5.37E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 1.00E-01 -1.04E-02 -1.11E-01
Schizophrenia 6A20 Prefrontal cortex 8.48E-01 1.65E-02 9.16E-02
Schizophrenia 6A20 Superior temporal cortex 6.33E-01 -3.44E-02 -3.98E-01
Scleroderma 4A42.Z Whole blood 3.64E-01 -3.91E-02 -3.16E-01
Seizure 8A60-8A6Z Whole blood 7.27E-01 1.38E-02 9.04E-02
Sensitive skin EK0Z Skin 4.05E-01 -2.20E-01 -1.02E+00
Sepsis with septic shock 1G41 Whole blood 3.07E-03 -3.84E-02 -1.80E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.30E-02 3.55E-01 1.25E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 8.39E-01 -4.00E-02 -2.58E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 7.43E-01 -5.33E-02 -4.09E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 7.19E-01 -8.36E-02 -3.68E-01
Skin cancer 2C30-2C3Z Skin 3.42E-06 -9.01E-02 -1.90E-01
Thrombocythemia 3B63 Whole blood 3.44E-01 1.67E-02 1.60E-01
Thrombocytopenia 3B64 Whole blood 7.18E-01 -2.49E-02 -9.07E-02
Thyroid cancer 2D10 Thyroid 1.36E-02 -6.10E-03 -1.73E-02
Tibial muscular dystrophy 8C75 Muscle tissue 7.85E-10 -4.09E-01 -3.48E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 6.47E-01 -5.67E-03 -4.99E-02
Type 2 diabetes 5A11 Liver tissue 9.91E-01 -1.42E-01 -5.10E-01
Ureter cancer 2C92 Urothelium 9.63E-01 -2.46E-03 -1.78E-02
Uterine cancer 2C78 Endometrium tissue 5.34E-04 4.82E-02 3.23E-01
Vitiligo ED63.0 Skin 6.21E-01 -6.65E-02 -2.97E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Aromatic-L-amino-acid decarboxylase (DDC) DTT Info
DME DTT Type Successful
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Carbidopa DMHRG8Q Parkinson disease 8A00.0 Approved [1]
Vitamin B6 DMDBZMV Vitamin B6 deficiency 5B5D Approved [2]
9 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Benserazide DMLU8NX N. A. N. A. Phase 3 [1]
Patrome DM3H2U4 Parkinson disease 8A00.0 Phase 3 [3]
AV-201 DMDL9WU Parkinson disease 8A00.0 Phase 2 [4]
GT-AADC DM8N3OQ Aromatic L-amino acid decarboxylase deficiency 5C59.00 Phase 2 [5]
PTC-AADC DM9ZHE3 Aromatic L-amino acid decarboxylase deficiency 5C59.00 Phase 2 [6]
VY-AADC DMPSBTL Parkinson disease 8A00.0 Phase 2 [7]
OXB-102 DMXF9DM Parkinson disease 8A00.0 Phase 1/2 [8]
ProSavin DMJ42E6 Parkinson disease 8A00.0 Phase 1/2 [9]
VY-AADC01 DM0N71R Parkinson disease 8A00.0 Phase 1 [10]
⏷ Show the Full List of 9 Clinical Trial Drug(s)
2 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
3-hydroxybenzylhydrazine DMNUM4K Discovery agent N.A. Investigative [11]
Noradrenalone (arterenone) DMFNB40 Discovery agent N.A. Investigative [12]

References

1 Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
2 Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 5;137B(1):1-4.
3 The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res. 2000 Nov;6(11):4365-72.
4 UCSF report
5 Clinical pipeline report, company report or official report of PTC Therapeutics.
6 ClinicalTrials.gov (NCT04903288) An Open-Label Trial to Address the Safety of the SmartFlow MR-Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Subjects. U.S.National Institutes of Health.
7 Clinical pipeline report, company report or official report of Voyager Therapeutics.
8 Clinical pipeline report, company report or official report of Oxford BioMedica.
9 Clinical pipeline report, company report or official report of Oxford BioMedica.
10 Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. Neurology. 2022 Jan 4;98(1):e40-e50.
11 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1271).
12 Activation of an adrenergic pro-drug through sequential stereoselective action of tandem target enzymes. Biochem Biophys Res Commun. 1992 Nov 30;189(1):33-9.
13 L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203.
14 Origin and metabolism of serotonin. J Cardiovasc Pharmacol. 1990;16 Suppl 3:S1-7.
15 Complexity of dopamine metabolism. Cell Commun Signal. 2013 May 17;11(1):34.