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Information on EC 4.1.1.28 - aromatic-L-amino-acid decarboxylase and Organism(s) Homo sapiens
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4.1.1.28 aromatic-L-amino-acid decarboxylaseIUBMB Comments
A pyridoxal-phosphate protein. The enzyme also acts on some other aromatic L-amino acids, including L-tryptophan, L-tyrosine and L-phenylalanine.
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Word Map
- 4.1.1.28
-
dopaminergic
- serotonin
- parkinsonism
-
monoamine
- striatum
- catecholamine
-
neurotransmitter
- carbidopa
- noradrenaline
- levodopa
- norepinephrine
- benserazide
- 5-hydroxytryptamine
-
substantia
-
dopac
-
serotonergic
- tryptamine
-
nigrostriatal
- catharanthus
- catechol-o-methyltransferase
- roseus
- beta-hydroxylase
-
5-hydroxyindoleacetic
-
homovanillic
-
3,4-dihydroxyphenylacetic
-
catecholaminergic
- dyskinesia
- dopamine-beta-hydroxylase
- alpha-methyl-p-tyrosine
-
5-hiaa
- pargyline
- strictosidine
-
monoaminergic
-
raphe
-
l-dopa-induced
- l-dihydroxyphenylalanine
- apomorphine
-
antiparkinsonian
- gamma-butyrolactone
-
tuberoinfundibular
-
autoreceptors
- 3-methoxytyramine
- quinpirole
- entacapone
-
catecholamine-synthesizing
-
dihydroxyphenylacetic
-
non-dopaminergic
- phenylethanolamine
- pharmacology
- analysis
-
6-hydroxydopamine-lesioned
- medicine
- drug development
- synthesis
- tolcapone
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dopa decarboxylase, aromatic l-amino acid decarboxylase, aromatic amino acid decarboxylase, tryptophan decarboxylase, l-dopa decarboxylase, l-aromatic amino acid decarboxylase, aromatic-l-amino-acid decarboxylase, l-amino-acid decarboxylase, 3,4-dihydroxyphenylalanine decarboxylase, aromatic l-aminoacid decarboxylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3,4-Dihydroxyphenylalanine decarboxylase
-
-
-
-
5-Hydroxy-L-tryptophan decarboxylase
-
-
-
-
5-Hydroxytryptophan decarboxylase
-
-
-
-
AADC
Aromatic amino acid decarboxylase
Aromatic L-amino acid decarboxylase
DDC
Decarboxylase, aromatic amino acid
-
-
-
-
Dihydroxyphenylalanine-5-hydroxytryptophan decarboxylase
-
-
-
-
DOPA DC
-
-
-
-
DOPA decarboxylase
DOPA-5-hydroxytryptophan decarboxylase
-
-
-
-
Hydroxytryptophan decarboxylase
-
-
-
-
L-3,4-Dihydroxyphenylalanine decarboxylase
L-5-Hydroxytryptophan decarboxylase
-
-
-
-
L-Aromatic amino acid decarboxylase
-
-
-
-
L-DOPA decarboxylase
L-Tryptophan decarboxylase
-
-
-
-
Tryptophan decarboxylase
TYDC
-
-
-
-
Tyrosine/Dopa decarboxylase
-
-
-
-
AADC
-
-
-
-
AADC
-
-
Aromatic amino acid decarboxylase
-
-
-
-
Aromatic L-amino acid decarboxylase
-
-
-
-
Aromatic L-amino acid decarboxylase
-
-
DDC
-
-
-
-
DDC
-
-
DDC
-
human DDC gene undergoes complex processing leading to the formation of multiple mRNA isoforms. Alternative splicing within its 5'-untranslated region leads to the formation of two mRNA types, neural (N1 exon) and non-neural (L1 exon) type. Neural type DDC transcript which lacks exon 3 and the alternative 37 kD alt-DDC protein isoform which lacks exons 10-15 but includes an alternative exon 10 in human peripheral leukocytes.
DOPA decarboxylase
-
-
-
-
DOPA decarboxylase
-
-
L-3,4-Dihydroxyphenylalanine decarboxylase
-
-
-
-
L-DOPA decarboxylase
-
-
-
-
L-DOPA decarboxylase
-
-
Tryptophan decarboxylase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
Pictet-Spengler cyclization
a reaction occurring at the active site of DDC
transamination
half-transamination of D-aromatic amino acid and aromatic amines under anaerobic conditions catalyzed by DDC
decarboxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
Aromatic-L-amino-acid carboxy-lyase
A pyridoxal-phosphate protein. The enzyme also acts on some other aromatic L-amino acids, including L-tryptophan, L-tyrosine and L-phenylalanine.
CAS REGISTRY NUMBER
COMMENTARY
9042-64-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
carbidopa
?
-
interaction of carbidopa with the Phe103 residue of the enzyme, the residue forms a displaced sandwich-type sigma-complex with carbidopa
-
-
?
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
neuroprotective role for AADC against L-DOPA toxicity in primary striatal cultures. The protective effect is due primarily to AADC-dependent conversion of L-DOPA to dopamine, leading, in turn, to an increase in intracellular dopamine levels
-
-
?
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
enzyme is involved in the biosynthesis of monoamine neurotransmitters
-
-
?
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
during the reaction with L-Dopa, monitored by stopped-flow spectrophotometry, a 420 nm band attributed to the 4'-N-protonated external aldimine first appears, and its decrease parallels the emergence of a 390 nm peak, assigned to the 4'-N-unprotonated external aldimine. The pH profile of the spectral change at 390 nm displays a pK of 6.4, which may represent the ESH(+) -> ES catalytic step
-
-
?
5-Hydroxytryptophan
Serotonin + CO2
-
The biosynthesis of serotonin requires aromatic substrates to be bound in the active sites of the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, AADC constitutes the last enzymatic step in the biosynthesis of dopamine
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
-
-
?
L-Dopa
dopamine + CO2
-
-
691469, 691846, 692661, 693374, 701921, 702954, 704803, 705265, 705269, 705756, 705914, 714634, 716172, 716342
-
-
?
L-Dopa
dopamine + CO2
-
enzyme is central in the synthesis of biogenic monoamine neurotransmitters, these include serotonin as well as the catecholamines dopamine and norepinephrine (noradrenaline)
-
-
?
L-Dopa
dopamine + CO2
-
second enzyme in the catecholamine biosynthetic pathway that catalyzes the synthesis of important neurotransmitters
-
-
?
L-Dopa
dopamine + CO2
substrate ionization is related to the catalytic event
-
-
?
additional information
?
-
-
the enzyme is responsible for the decarboxylation step in both the catecholamine and the indolamine synthetic pathways. The enzyme is regulated by a short term mechanism that may involve activation of adenyl cyclase or protein kinase C
-
-
?
additional information
?
-
-
AADC deficiency leads to severe floppiness, oculogyric crises, athetoid movement, prominent startle response, tongue thrusting, ptosis, paroxysmal diaphoresis, nasal congestion, diarrhea, irritability and sleep disorders, patients with AADC deficiency in Taiwan have particular clinical manifestations of small hands and feet
-
-
?
additional information
?
-
-
AADC follows the initial and rate-limiting step of synthesis, which is the formation of levodopa and 5-hydroxytryptophan from tyrosine and tryptophan by specific tetrahydrobiopterin-dependent hydroxylases
-
-
?
additional information
?
-
-
Aromatic L-amino acid decarboxylase deficiency is a disorder of biogenic amine metabolism resulting in generalized combined deficiency of serotonin, dopamine and catecholamines. Main clinical features are developmental delay, muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms
-
-
?
additional information
?
-
-
aromatic L-amino acid decarboxylase deficiency is a rare inborn error of neurotransmitter biosynthesis that leads to a combined deficiency of catecholamines and serotonin and is characterized by global developmental delay, involuntary movements, and autonomic dysfunction
-
-
?
additional information
?
-
-
deficiency of the enzyme leads to a reduced level of downstream biogenic amines, including dopamine, norepinephrine, epinephrine and serotonin, which plays a potential pathophysiological role in disorders of psychomotor modulation, maladjustment in sleep pattern, body temperature, cardiovascular, respiratory, and gastrointestinal systems
-
-
?
additional information
?
-
-
L-dopa decarboxylase is a pyridoxal 5'-phosphate-dependent enzyme involved in many malignancies
-
-
?
additional information
?
-
-
Mutations that decrease substrate binding can result in a decrease in serotonin production and thus can lead to depression and related disorders
-
-
?
additional information
?
-
-
regulating factor of the proliferation and differentiation of different leukocyte subtypes
-
-
?
additional information
?
-
-
tyrosine hydroxylase mRNA and DDC mRNA in plasma of children with neuroblastoma are highly correlated
-
-
?
additional information
?
-
under all reaction conditions tested, the enzyme fails to catalyze thyroid hormone decarboxylation. The enzyme is responsible for Thyronamine biosynthesis via decarboxylation of thyroid hormone
-
-
?
additional information
?
-
-
under all reaction conditions tested, the enzyme fails to catalyze thyroid hormone decarboxylation. The enzyme is responsible for Thyronamine biosynthesis via decarboxylation of thyroid hormone
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
neuroprotective role for AADC against L-DOPA toxicity in primary striatal cultures. The protective effect is due primarily to AADC-dependent conversion of L-DOPA to dopamine, leading, in turn, to an increase in intracellular dopamine levels
-
-
?
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
enzyme is involved in the biosynthesis of monoamine neurotransmitters
-
-
?
5-Hydroxytryptophan
Serotonin + CO2
-
The biosynthesis of serotonin requires aromatic substrates to be bound in the active sites of the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, AADC constitutes the last enzymatic step in the biosynthesis of dopamine
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
-
-
?
L-Dopa
dopamine + CO2
-
-
-
-
?
L-Dopa
dopamine + CO2
-
enzyme is central in the synthesis of biogenic monoamine neurotransmitters, these include serotonin as well as the catecholamines dopamine and norepinephrine (noradrenaline)
-
-
?
L-Dopa
dopamine + CO2
-
second enzyme in the catecholamine biosynthetic pathway that catalyzes the synthesis of important neurotransmitters
-
-
?
additional information
?
-
-
the enzyme is responsible for the decarboxylation step in both the catecholamine and the indolamine synthetic pathways. The enzyme is regulated by a short term mechanism that may involve activation of adenyl cyclase or protein kinase C
-
-
?
additional information
?
-
-
AADC deficiency leads to severe floppiness, oculogyric crises, athetoid movement, prominent startle response, tongue thrusting, ptosis, paroxysmal diaphoresis, nasal congestion, diarrhea, irritability and sleep disorders, patients with AADC deficiency in Taiwan have particular clinical manifestations of small hands and feet
-
-
?
additional information
?
-
-
AADC follows the initial and rate-limiting step of synthesis, which is the formation of levodopa and 5-hydroxytryptophan from tyrosine and tryptophan by specific tetrahydrobiopterin-dependent hydroxylases
-
-
?
additional information
?
-
-
Aromatic L-amino acid decarboxylase deficiency is a disorder of biogenic amine metabolism resulting in generalized combined deficiency of serotonin, dopamine and catecholamines. Main clinical features are developmental delay, muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms
-
-
?
additional information
?
-
-
aromatic L-amino acid decarboxylase deficiency is a rare inborn error of neurotransmitter biosynthesis that leads to a combined deficiency of catecholamines and serotonin and is characterized by global developmental delay, involuntary movements, and autonomic dysfunction
-
-
?
additional information
?
-
-
deficiency of the enzyme leads to a reduced level of downstream biogenic amines, including dopamine, norepinephrine, epinephrine and serotonin, which plays a potential pathophysiological role in disorders of psychomotor modulation, maladjustment in sleep pattern, body temperature, cardiovascular, respiratory, and gastrointestinal systems
-
-
?
additional information
?
-
-
L-dopa decarboxylase is a pyridoxal 5'-phosphate-dependent enzyme involved in many malignancies
-
-
?
additional information
?
-
-
Mutations that decrease substrate binding can result in a decrease in serotonin production and thus can lead to depression and related disorders
-
-
?
additional information
?
-
-
regulating factor of the proliferation and differentiation of different leukocyte subtypes
-
-
?
additional information
?
-
-
tyrosine hydroxylase mRNA and DDC mRNA in plasma of children with neuroblastoma are highly correlated
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
(vitamin B6), patients with AAAD deficiency receives a therapeutic trial with pyridoxal-5'-phosphate, individual dosage varies between 150 and 4800 mg/day (20-160 mg/kg per day). 4 of 9 patients improved slightly on vitamin B6 (3 of them are siblings with a special L-dopa responsive mutation). There is no change in CSF neurotransmitter findings in all investigated patients. Side effects are predominantly gastrointestinal, such as nausea, vomiting and abdominal pain.
pyridoxal 5'-phosphate
-
essential cofactor, pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase
pyridoxal 5'-phosphate
-
the essential cofactor stabilizes and enhances enzymatic activity
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
increasing concentrations of Zn2+ result in a raise in the solubilization of the membrane-associated enzyme, while the presence of increasing concentrations of Ca2+ and Mg2+ inhibits enzyme release from the MF sample
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-[1-[4-hydroxy-5-[3-(3-hydroxy-4-methoxyphenyl)propyl]-2-methoxyphenyl]-3-(4-hydroxy-3-methoxyphenyl)propyl]-5-methoxycyclohexa-2,5-diene-1,4-dione
-
inhibitor isolated from Euonymus glabra Roxb.
2-[[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)sulfonyl]amino]-N-phenylbenzamide
-
competitive. Inhibitor is unable to bind free pyridoxal 5'-phosphate, and predicted to not cross the blood-brain barrier
3,4-dihydroxyphenylalanine
-
inhibitory effect of 3,4-dihydroxyphenylalanine on the conversion of 5-hydroxy-L-tryptophan
3-[2-hydroxy-5-[3-(4-hydroxy-3-methoxyphenyl)propyl]-4-methoxyphenyl]-2-[3-(4-hydroxy-3-methoxyphenyl)-2-oxopropyl]-5-methoxycyclohexa-2,5-diene-1,4-dione
-
inhibitor isolated from Euonymus glabra Roxb., structural analogue of dopamine. Compound is able to suppress the activity of dopa decarboxylase and dopamine levels in purified enzyme and cell-based assays
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2,3-triol
-
mixed type inhibition. Inhibitor is unable to bind free pyridoxal 5'-phosphate, and predicted to not cross the blood-brain barrier
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2-diol
-
competitive. Inhibitor is unable to bind free pyridoxal 5'-phosphate, and predicted to not cross the blood-brain barrier
4-[(E)-[[3-(4-chlorophenyl)-5-sulfanyl-4H-1,2,4-triazol-4-yl]imino]methyl]benzene-1,2-diol
-
competitive. Inhibitor is unable to bind free pyridoxal 5'-phosphate, and predicted to not cross the blood-brain barrier
5-hydroxy indole acetic acid
-
the conversion of 5-hydroxy-L-tryptophan is 20% inhibited by 0.33 mM 5-hydroxy indole acetic acid
5-hydroxy-L-tryptophan
-
strong inhibitory effect of 5-hydroxy-L-tryptophan on the conversion of 3,4-dihydroxyphenylalanine
epigallocatechin-3-gallate
EGCG, the inhibitory effect is mediated by blocking the entrance to the catalytic site, therefore, preventing substrate binding
serotonin
and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition
Benserazide
-
competitive inhibitor of L-Dopa, but a non-competitive inhibitor of 5-hydroxytryptophan
carbidopa
-
strongly inhibited by increasing concentrations of carbidopa, at a concentration of 0.4 mM carbidopa the conversion of 3,4-dihydroxyphenylalanine is completely inhibited, at a concentration of 0.25 mM the conversion of 5-hydroxy-L-tryptophan is completely inhibited
carbidopa
the compound is able to block the reaction at the Michaelis complex step in DDC
dopamine
-
the conversion of 5-hydroxy-L-tryptophan is strongly inhibited by dopamine
L-Dopa
-
20.3% decrease in activity in corpus striatum following a 2 years treatment
L-Dopa
-
slight substrate inhibition is observed at high concentration of L-Dopa
additional information
-
not inhibited by 3-methoxy-tyrosine, homovanillic acid, or 5-hydroxy-tryptamine
-
additional information
-
diminished AAAD activity in dopaminergic cells that overexpress alpha-sinuclein
-
additional information
-
increasing concentrations of the serine protease inhibitor aprotinin have a minimal inhibitory effect on enzyme solubilization while leupeptin inhibits release of membrane-bound enzyme
-
additional information
-
4-benzoquinone might be the crucial chemical moiety for binding and inhibiting human DOPA decarboxylase
-
additional information
the inhibitory principle is based on a hydrazine group that forms a hydrazone derivative with pyridoxal 5'-phosphate, thus blocking it and inactivating the enzyme. Thus, a greater amount of L-Dopa can reach the brain where it can be transformed to dopamine ameliorating disease symptoms. Compounds acting via a suicide mechanism by alkylating the enzyme: alpha-chloromethyl and alpha-fluoromethyl derivatives of Dopa, alpha-vinyl-Dopa and alpha-acetylenic Dopa. The phosphopyridoxyl aromatic amino acids Schiff base analogues and substrate analogues, like green tea polyphenols, also inhibit the enzyme
-
additional information
successful strategies to inhibit the decarboxylase have included the synthesis of fluoro-derivatives, which act as competitive and/or suicide inhibitors, as it is the case of several fluoro-dopa derivatives
-
additional information
-
successful strategies to inhibit the decarboxylase have included the synthesis of fluoro-derivatives, which act as competitive and/or suicide inhibitors, as it is the case of several fluoro-dopa derivatives
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
haloperidol
-
enhanced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor antagonist
additional information
-
activation in vivo occurs in response to the acute action of physiological stimuli, drugs that act at neurotransmitter receptors, or modulation of the activity of endogenous kinases and phospatases
-
additional information
-
DDC is overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients. High expression levels of DDC are found more frequently in high Gleason's score tumors as well as in advanced stage patients.
-
additional information
-
high expression of DDC in blood and bone marrow corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome
-
additional information
-
relative to obtained dose of Adeno-associated virus type 2 including human AADC gene, high dose-dependent levels of cDNA are detected
-
additional information
-
the early activation of AAAD is followed by a late, longer lasting (hours) response, which is accompanied by an increase of mRNA and protein
-
additional information
-
pyridoxal 5'-phosphate deficiency reduces AADC activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.49
5-hydroxy-L-tryptophan
-
in 167 mM phosphate buffer, pH 7.0, containing 39 mM dithiotreitol and 0.167 mM NaEDTA, for 2 h at 37°C
0.62
3,4-dihydroxyphenylalanine
-
in 167 mM phosphate buffer, pH 7.0, containing 39 mM dithiotreitol and 0.167 mM NaEDTA, for 2 h at 37°C
0.047
L-5-hydroxytryptophan
-
in the presence of 0.07 mM pyridoxal 5'-phosphate, in 167 mM sodium phosphate pH 8.0, at 37°C
0.000095
L-Dopa
-
dopamine formation, mutant enzyme K303A, in 50 mM HEPES, pH 7.5, at 25°C
0.00092
L-Dopa
-
aldehyde formation, mutant enzyme K303A, in 50 mM HEPES, pH 7.5, at 25°C
0.028
L-Dopa
decarboxylation reaction, pH and temperature not specified in the publication
0.307
L-Dopa
-
in the absence of pyridoxal 5'-phosphate, in 500 mM sodium phosphate pH 7.0, at 37°C
0.333
L-Dopa
-
in the presence of 0.07 mM pyridoxal 5'-phosphate, in 500 mM sodium phosphate pH 7.0, at 37°C
additional information
additional information
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.11
L-Dopa
-
aldehyde formation, mutant enzyme K303A, in 50 mM HEPES, pH 7.5, at 25°C
0.188
L-Dopa
-
dopamine formation, mutant enzyme K303A, in 50 mM HEPES, pH 7.5, at 25°C
5.1
L-Dopa
decarboxylation reaction, pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0044
2-[[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)sulfonyl]amino]-N-phenylbenzamide
-
pH 7.4, 25°C
0.0151
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2,3-triol
-
pH 7.4, 25°C
0.0018
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2-diol
-
pH 7.4, 25°C
0.0023
4-[(E)-[[3-(4-chlorophenyl)-5-sulfanyl-4H-1,2,4-triazol-4-yl]imino]methyl]benzene-1,2-diol
-
pH 7.4, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0216
2-[1-[4-hydroxy-5-[3-(3-hydroxy-4-methoxyphenyl)propyl]-2-methoxyphenyl]-3-(4-hydroxy-3-methoxyphenyl)propyl]-5-methoxycyclohexa-2,5-diene-1,4-dione
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0168
2-[[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)sulfonyl]amino]-N-phenylbenzamide
Homo sapiens
-
pH 7.4, 25°C
0.0115
3-[2-hydroxy-5-[3-(4-hydroxy-3-methoxyphenyl)propyl]-4-methoxyphenyl]-2-[3-(4-hydroxy-3-methoxyphenyl)-2-oxopropyl]-5-methoxycyclohexa-2,5-diene-1,4-dione
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0067
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2,3-triol
Homo sapiens
-
pH 7.4, 25°C
0.002 - 4
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2-diol
Homo sapiens
-
pH 7.4, 25°C
0.0063
4-[(E)-[[3-(4-chlorophenyl)-5-sulfanyl-4H-1,2,4-triazol-4-yl]imino]methyl]benzene-1,2-diol
Homo sapiens
-
pH 7.4, 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00003
-
enzyme from HTB-14 cells, at 37°C, pH not specified in the publication
3.67
-
activity in peripheral leukocytes, determined by radiochemical method at 37°C
additional information
additional information
-
specific activity 490 U/mg, enzyme activity is expressed in nanomole of substrate transformed per minute per milliliter of enzyme preparation
additional information
-
after gene transfer in nondegenerating striatal neurons in patients, transgene expression of AADC can be monitored in the putamen
additional information
-
altered enzyme activity and regulation contributes to the decreasing therapeutic response of L-dopa
additional information
-
although the obtained specific activity values are found to be lower than the activity values observed in embryonic K293 cells, the data strongly suggest the endogenous dopamine production in these types of cells and underline the complexity of the dopamine synthetic pathway
additional information
-
enzyme activity is 0 pmol/ml plasma per min, patient 4 with AAAD deficiency (reference range 33-79 pmol/ml plasma per min)
additional information
-
enzyme activity is 0 pmol/ml plasma per min, patient 7 with AAAD deficiency (reference range 23-34 pmol/ml plasma per min)
additional information
-
enzyme activity is 0 pmol/ml plasma per min, patient 9 with AAAD deficiency (reference range 23-34 pmol/ml plasma per min)
additional information
-
enzyme activity is 0.2 pmol/ml plasma per min, patient 1 with AAAD deficiency (reference range 47-119 pmol/ml plasma per min)
additional information
-
enzyme activity is 0.6 pmol/ml plasma per min, patient 3 with AAAD deficiency (reference range 33-79 pmol/ml plasma per min)
additional information
-
enzyme activity is 0.6 pmol/ml plasma per min, patient 8 with AAAD deficiency (reference range 23-34 pmol/ml plasma per min)
additional information
-
enzyme activity is 1.6 pmol/ml plasma per min, patient 6 with AAAD deficiency (reference range 36-129 pmol/ml plasma per min)
additional information
-
enzyme activity is 4.0 pmol/ml plasma per min, patient 5 with AAAD deficiency (reference range 47-119 pmol/ml plasma per min)
additional information
-
enzyme activity is below 1 U/l plasma, patient 2 with AAAD deficiency (reference range 18-34 pmol/ml plasma per min)
additional information
-
enzyme activity is closely associated with substrate response and is a determining factor for the formation of dopamine
additional information
-
the purified enzyme shows a specific activity of 3.67 units/mg at 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
4222, 4225, 4226, 4228, 665125, 666118, 666447, 677950, 680090, 681067, 681181, 681865, 681948, 691469, 691846, 691888, 691987, 692189, 692661, 693374, 693490, 694368, 701921, 702954, 704803, 705265, 705269, 705756, 705914, 714634, 716172, 716342, 726553, 727123
-
-
heterozygous for mutation G102S, mutation decreases the binding affinity for the substrate, clinical phenotype caused by aromatic L-amino acid decarboxylase deficiency
-
-
Macaca mulatta with parkinsonian syndrome, infused with different doses of adeno-associated virus type 2 including human AADC gene
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
high DDC mRNA expression levels are found in well-differentiated and Dukes' stage A and B tumors
-
expression of neural-type and non-neural DDC isoforms, although HeLa cells express full length and the alternative Alt-DDC isoforms, they do not possess enzymatic activity towards the decarboxylation of L-Dopa
-
IMR 32, CHP-212, SH-SY5Y, SK-N-SH, SK-N-FI, SK-N-AS, SK-N-BE(2) and SK-N-DZ
-
total RNA is isolated from tissue specimens from benign prostate hyperplasia and prostate cancer patients
additional information
additional information
-
tissue specificity is proposed to be directed by both alternative promoter usage and alternative splicing
additional information
neuronal and non-neuronal tissues express DDC mRNAs with distinct 5'-UTR due to alternative promotor usage and alternative splicing within the 5'-UTR. Different splicing variants are observed in cancer cells. The human DDC gene is highly expressed in substantia nigra, terminal ileum,colon transverse, kidney cortex, liver, and pancreas
additional information
-
neuronal and non-neuronal tissues express DDC mRNAs with distinct 5'-UTR due to alternative promotor usage and alternative splicing within the 5'-UTR. Different splicing variants are observed in cancer cells. The human DDC gene is highly expressed in substantia nigra, terminal ileum,colon transverse, kidney cortex, liver, and pancreas
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
a significant number of proteins exist in membrane-associated and soluble forms
-
additional information
the enzyme is associated with the membrane in dopamine pro-ducing cells such as neurons, leukocytes and kidney cancer cells
-
additional information
-
the enzyme is associated with the membrane in dopamine pro-ducing cells such as neurons, leukocytes and kidney cancer cells
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
-
AADC deficiency is an autosomal recessive disorder caused by mutations in the AADC gene leading to severely reduced AADC activity. The condition presents early in life and is characterized by axial hypotonia, hypokinesia, choreoathetosis, developmentaldelay and episodes of dystonia, limb hypertonia and oculogyric crises
malfunction
-
aromatic L-amino acid decarboxylase deficiency is characterized by oculogyric crises, paroxysmal dystonic attacks, and severe psychomotor retardation since early infancy
malfunction
-
aromatic L-amino acid decarboxylase (AADC) deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder caused by a deficit of the AADC that is involved in serotonin and dopamine biosynthesis, causing serotonin and dopamine deficits, but also a lack of norepinephrine and epinephrine, given that dopamine is their precursor. The mutation S250F causes permanent dystonic posture at the 4 limbs with numbness and tingling, diplopia, and low potassium levels, mood problems, fever, bradycardia alternating with atrial and ventricular fibrillation, loss of consciousness, involuntary parossistic eye and head movements, bilateral ptosis, oculogyric crises with dystonia of the head, muscle hypotrophy, and absent deep tendon reflexes. The phenotypic spectrum of AADCD is broad and can range from very severe to relatively mild, overview
malfunction
gene-disease associations and common pathologies, detailed overview
physiological function
mammalian Dopa decarboxylase catalyzes the conversion of L-Dopa and L-5 hydroxytryptophan to dopamine and serotonin, respectively. Both of them are biologically active neurotransmitters whose levels has to be finely tuned. An altered concentration of dopamine is the cause of neurodegenerative diseases, such as Parkinson's disease. Enzyme DDC is not considered to be rate-limiting in physiological catecholamines or indoleamines synthesis, but it becomes rate-limiting in several pathological states related to aberrant dopamine production, such as Parkinson's disease (PD) or the bipolar syndrome. PD is a chronic progressive neurological disorder characterized by tremor, bradykinesia, rigidity and postural instability. These symptons are caused by the low levels of dopamine resulting from the degeneration of dopamine-producing cells in the substantia nigra of the brain
physiological function
the enzyme is responsible for the biosynthesis of dopamine. It is involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. Memory seems to be an important physiological function involving histamine, dopamine, and serotonin
additional information
structural and functional analogies and differences between histidine decarboxylase (EC 4.1.1.22) and aromatic L-amino acid decarboxylase molecular networks, overview. Human histidine decarboxylase (HDC) and dopa decarboxylase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively
additional information
-
structural and functional analogies and differences between histidine decarboxylase (EC 4.1.1.22) and aromatic L-amino acid decarboxylase molecular networks, overview. Human histidine decarboxylase (HDC) and dopa decarboxylase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DDC_HUMAN
480
0
53926
Swiss-Prot
other Location (Reliability: 3)
A0A3S5WLQ3_HUMAN
363
0
40993
TrEMBL
other Location (Reliability: 3)
A0A3S6CJ90_HUMAN
408
0
45675
TrEMBL
other Location (Reliability: 3)
A0A3S6CLD8_HUMAN
413
0
45752
TrEMBL
other Location (Reliability: 3)
A0A3S6CS78_HUMAN
290
0
32622
TrEMBL
other Location (Reliability: 2)
A0A3S5XFR7_HUMAN
357
0
40797
TrEMBL
other Location (Reliability: 2)
A0A3S5X9I4_HUMAN
405
0
45791
TrEMBL
other Location (Reliability: 2)
A0A3S6CS67_HUMAN
446
0
49904
TrEMBL
other Location (Reliability: 3)
A0A3Q8A2M4_HUMAN
401
0
45222
TrEMBL
other Location (Reliability: 3)
A0A3S5WLQ6_HUMAN
362
0
40557
TrEMBL
other Location (Reliability: 3)
A0A3Q7ZZZ7_HUMAN
287
0
32310
TrEMBL
other Location (Reliability: 2)
A0A3S6CLE2_HUMAN
273
0
31076
TrEMBL
other Location (Reliability: 3)
A0A3S6D691_HUMAN
398
0
44910
TrEMBL
other Location (Reliability: 3)
A0A3S5X9I6_HUMAN
202
0
22695
TrEMBL
other Location (Reliability: 3)
A0A3S5X9H5_HUMAN
330
0
36841
TrEMBL
other Location (Reliability: 3)
A0A3S6CN46_HUMAN
335
0
37304
TrEMBL
other Location (Reliability: 2)
A0A3Q8A2K4_HUMAN
360
0
40681
TrEMBL
other Location (Reliability: 3)
A0A3S6CVQ1_HUMAN
352
0
39792
TrEMBL
other Location (Reliability: 3)
A0A3Q8A2L5_HUMAN
400
0
44786
TrEMBL
other Location (Reliability: 3)
A0A3S6CN52_HUMAN
235
0
26847
TrEMBL
other Location (Reliability: 3)
A0A3S6CYS1_HUMAN
327
0
36529
TrEMBL
other Location (Reliability: 3)
A0A3S7HNV4_HUMAN
365
0
40758
TrEMBL
other Location (Reliability: 3)
A0A3Q7ZZZ2_HUMAN
483
0
54239
TrEMBL
other Location (Reliability: 3)
A0A3Q8A018_HUMAN
375
0
41523
TrEMBL
other Location (Reliability: 3)
A0A3Q7ZZY9_HUMAN
323
0
36774
TrEMBL
other Location (Reliability: 2)
A0A3S6D699_HUMAN
314
0
35563
TrEMBL
other Location (Reliability: 3)
A0A3S6CPK2_HUMAN
368
0
41070
TrEMBL
other Location (Reliability: 3)
A0A3S6CPU7_HUMAN
411
0
45987
TrEMBL
other Location (Reliability: 3)
A0A3S6CVP2_HUMAN
368
0
41456
TrEMBL
other Location (Reliability: 2)
A0A3S6CPV2_HUMAN
274
0
31344
TrEMBL
other Location (Reliability: 2)
A0A3S5X9H4_HUMAN
320
0
36462
TrEMBL
other Location (Reliability: 2)
A0A3Q8A2N0_HUMAN
240
0
26924
TrEMBL
other Location (Reliability: 3)
A0A3S5X9H9_HUMAN
378
0
41835
TrEMBL
other Location (Reliability: 3)
A0A3Q7ZYN3_HUMAN
371
0
41768
TrEMBL
other Location (Reliability: 2)
A0A3S6CJ93_HUMAN
338
0
37616
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37000
50000
54000
55000
37000
-
determined by SDS-PAGE, determined by SDS-PAGE, expression of the alternative DDC molecule (alt-DDC) in human peripheral leukocytes, lacks exons 10-15 but includes an alternative exon 10
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
additional information
additional information
a 150 amino acid long C-terminal region is present in mammalian HDC but absent in homologous Gram-negative bacteria HDC and all mammalian DDCs
additional information
-
a 150 amino acid long C-terminal region is present in mammalian HDC but absent in homologous Gram-negative bacteria HDC and all mammalian DDCs
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apoenzyme, to 2.9 A resolution. The apoenzyme exists in an unexpected open conformation. Compared to the pig kidney holoenzyme, the dimer subunits move 20 A apart and the two active sites become solvent exposed. Complete achievement of the closed conformation of the dimer is not essential for Schiff base formation and pyridoxal 5'-phosphate binding to the intermediate monomer is able to induce rearrangement of loop1. Covalent binding of the cofactor can only be achieved after an initial rearrangement towards the closed conformation
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A275T
naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency
A91V
naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency
E227A/R228A/D229A/K230A
-
replacement of amino acids 227-230 (ERDK) with alanine residues reduces reactivity to 13.6% compared to the wild type enzyme
F309L
naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency
G102S
naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency
K303A
-
the mutant binds pyridoxal 5'-phosphate with a 100fold decreased apparent equilibrium binding affinity with respect to the wild type enzyme. Unlike the wild-type, K303A in the presence of L-Dopa displays a parallel progress course of formation of both dopamine and 3,4-dihydroxyphenylacetaldehyde (plus ammonia) with a burst followed by a linear phase
R347Q
naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency
S147R
naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency
S250F
V614A
additional information
-
Model chemistry by second-order Moller-Plessett perturbation theory calculations, phenylalanine in position 103 is replaced by all native amino acids. The mutant residues which conserve an aromatic side chain (tyrosine and tryptophan) retain near 100% interaction energy with the carbidopa, and thus most likely retain full protein function. Arginine has an interaction energy of 555% of the wild-type. This is due to the fact that the long, polar side chain is able to find a geometry where a hydrogen bond is being made with the hydroxyl group of the carbidopa. The small side chains are not close enough to the carbidopa to have a large deal of dispersion/induction interactions. Residues are arranged by the size of the side chain, and with a few exception, the interaction energy generally increases with size of the side chain. Glycine, alanine, serine, threonine, and histidine all fall below the above mentioned 20% threshold and would likely cause a loss of protein function. Serine contains a polar side chain and histidine has pi-electrons, yet these residues are too small and too far removed to have strong interactions.
S250F
-
c.749C>T, naturally occuring mutation in enzyme DDC involved in the rare, autosomal recessive neurometabolic disorder of aromatic L-amino acid decarboxylase (AADC) deficiency (AADCD), lethal phenotype, detailed overview
S250F
naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
neither pyridoxal 5-phosphate deficiency nor the addition of 4-deoxypyridoxine affected aromatic L-amino acid decarboxylase stability over 8 h with protein synthesis inhibited.
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease
-
developed an adeno-associated virus vector that contains human AADC cDNA under the control of the cytomegalovirus promoter. Infusion of this vector into the striatum of parkinsonian rats and monkeys improves L-DOPA responsiveness by improving AADC-mediated conversion of L-DOPA to dopamine
-
expression in Escherichia coli
gene ddc, located on chromosome 7p12.2, sequence comparisons, in addition to a TATA box, a strong promoter is detectedin the human DDC gene. It contains three positive regulatory elements located from position -560 bp to -1. Another two negative regulatory cis-elements are detected in between -9000 and 560 and 396-31. An alternative-promoter mechanism for regulating tissue-specific expression of DDC gene is observed
human AADC gene is cloned into a Adeno-associated virus type 2 shuttle plasmid, and a recombinant Adeno-associated virus type 2 containing hAADC under the control of the cytomegalovirus promoter is generated by a triple transfection technique
-
in a primate model of Parkinson disease, intrastriatal infusion of an adeno-associated viral vector containing the AADC gene results in robust gene expression
-
splice variant of L-Dopa decarboxylase lacking exons 10-15 of the full-length transcript but includes an alternative exon 10
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DDC mRNA is transcribed in two different forms, neural and non-neural, due to alternative promoter usage and alternative splicing within the 5'-untranslated region
-
in lung, DDC expression in neuroendocrine differentiated cells is upregulated by Notch-1 receptor-elicited signaling
pyridoxal 5'-phosphate-deficient human SH-SY5Y neuroblastoma cells exhibit reduced levels of aromatic L-amino acid decarboxylase activity and protein but with no alteration in expression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
pharmacology
biosynthesis of pharmaceutically important monoterpenoid indole alkaloids
drug development
-
Parkinson disease, gene therapy, initiation of a phase I safety trial
drug development
the enzyme is a target for drug development in the therapy of either Parkinson's disease or aromatic amino acid decarboxylase deficiency
medicine
-
coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease
medicine
-
Because epileptic attacks can be treated with appropriate antiepileptic drugs, a confirmation whether patients with AADC deficiency have both non-epileptic and epileptic seizures in varying proportions, is necessary. The differentiation of epileptic seizures from involuntary non-epileptic movements, such as short-lasting dystonic attacks, chorea, or myoclonus, is indispensable for the adequate treatment of patients with AADC deficiency.
medicine
-
combination treatment of Adeno-associated virus type-2 containing human AADC gene, with oral levodopa is a novel therapeutic approach in patients with Parkinson disease
medicine
-
Development of therapy of patients with aromatic L-amino acid decarboxylase deficiency. Drug therapy in patients with AADC deficiency aims at correcting the central and peripheral deficiency of serotonin and catecholamines. Treatment is very challenging. There are no established treatment schemes or clear dosages for the individual drugs.
medicine
-
diagnosis of neuroblastoma, both tyrosine hydroxylase mRNA and DDC mRNA could be useful for stratifying patients into different treatment groups in future clinical trials.
medicine
-
potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer
medicine
-
there is no association between single nucleotide polymorphisms in the DDC gene and suicidal behavior
medicine
-
DDC mRNA expression is a potential tissue biomarker in colorectal adenocarcinoma
medicine
enzyme is responsible for thyronamine biosynthesis via decarboxylation of thyroid hormone. In addition, patients with aromatic L-amino acid decarboxylase-deficiency display thyronamines in plasma at levels similar to those of healthy controls
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhu, M.Y.; Juorio, A.V.
Aromatic L-amino acid decarboxylase: biological characterization and functional role
Gen. Pharmacol.
26
681-696
1995
Bos taurus, Cavia porcellus, Homo sapiens, Rattus norvegicus, Sus scrofa, Xenopus laevis
Nasrin, S.; Ichinose, H.; Nagatsu, T.
Comparison and characteristics of bovine aromatic L-amino acid decarboxylase with human enzyme
Biochim. Biophys. Acta
1118
318-322
1992
Bos taurus, Homo sapiens
Sumi, C.; Ichinose, H.; Nagatsu, T.
Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells
J. Neurochem.
55
1075-1078
1990
Homo sapiens
Mappouras, D.G.; Stiakakis, J.; Fragoulis, E.G.
Purification and characterization of L-DOPA decarboxylase from human kidney
Mol. Cell. Biochem.
94
147-156
1990
Homo sapiens
Siaterli, M.Z.; Vassilacopoulou, D.; Fragoulis, E.G.
Cloning and expression of human placental L-Dopa decarboxylase
Neurochem. Res.
28
797-803
2003
Homo sapiens
Facchini, P.J.; Huber-Allanach, K.L.; Tari, L.W.
Plant aromatic L-amino acid decarboxylases: evolution, biochemistry, regulation, and metabolic engineering applications
Phytochemistry
54
121-138
2000
Cinchona calisaya, Drosophila melanogaster, Solanum lycopersicum, Sus scrofa, Cinchona officinalis, Catharanthus roseus (P17770), Homo sapiens (P20711), Camptotheca acuminata (P93082)
Chang, Y.T.; Sharma, R.; Marsh, J.L.; McPherson, J.D.; Bedell, J.A.; Knust, A.; Brautigam, C.; Hoffmann, G.F.; Hyland, K.
Levodopa-responsive aromatic L-amino acid decarboxylase deficiency
Ann. Neurol.
55
435-438
2004
Homo sapiens
Sun, M.; Kong, L.; Wang, X.; Holmes, C.; Gao, Q.; Zhang, G.R.; Pfeilschifter, J.; Goldstein, D.S.; Geller, A.I.
Coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease
Hum. Gene Ther.
15
1177-1196
2004
Homo sapiens
Doroudchi, M.M.; Liauw, J.; Heaton, K.; Zhen, Z.; Forsayeth, J.R.
Adeno-associated virus-mediated gene transfer of human aromatic L-amino acid decarboxylase protects mixed striatal primary cultures from L-DOPA toxicity
J. Neurochem.
93
634-640
2005
Homo sapiens
Vassilacopoulou, D.; Sideris, D.C.; Vassiliou, A.G.; Fragoulis, E.G.
Identification and characterization of a novel form of the human L-dopa decarboxylase mRNA
Neurochem. Res.
29
1817-1823
2004
Homo sapiens
Bratland, E.; Wolff, A.S.; Haavik, J.; Kaempe, O.; Skoeldberg, F.; Perheentupa, J.; Bredholt, G.; Knappskog, P.M.; Husebye, E.S.
Epitope mapping of human aromatic L-amino acid decarboxylase
Biochem. Biophys. Res. Commun.
353
692-698
2007
Homo sapiens
Wafa, L.A.; Palmer, J.; Fazli, L.; Hurtado-Coll, A.; Bell, R.H.; Nelson, C.C.; Gleave, M.E.; Cox, M.E.; Rennie, P.S.
Comprehensive expression analysis of L-dopa decarboxylase and established neuroendocrine markers in neoadjuvant hormone-treated versus varying Gleason grade prostate tumors
Hum. Pathol.
38
161-170
2007
Homo sapiens
Candeloro, P.; Voltattorni, C.B.; Perniola, R.; Bertoldi, M.; Betterle, C.; Mannelli, M.; Giordano, R.; De Bellis, A.; Tiberti, C.; Laureti, S.; Santeusanio, F.; Falorni, A.
Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase
J. Clin. Endocrinol. Metab.
92
1096-1105
2007
Homo sapiens
Uccella, S.; Cerutti, R.; Vigetti, D.; Furlan, D.; Oldrini, R.; Carnevali, I.; Pelosi, G.; La Rosa, S.; Passi, A.; Capella, C.
Histidine decarboxylase, DOPA decarboxylase, and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis
J. Histochem. Cytochem.
54
863-875
2006
Homo sapiens
Margiotti, K.; Wafa, L.A.; Cheng, H.; Novelli, G.; Nelson, C.C.; Rennie, P.S.
Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells
Mol. Cancer
6
38
2007
Homo sapiens
Verbeek, M.M.; Geurtz, P.B.; Willemsen, M.A.; Wevers, R.A.
Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes
Mol. Genet. Metab.
90
363-369
2007
Homo sapiens
Kokkinou, I.; Nikolouzou, E.; Hatzimanolis, A.; Fragoulis, E.G.; Vassilacopoulou, D.
Expression of enzymatically active L-DOPA decarboxylase in human peripheral leukocytes
Blood Cells Mol. Dis.
42
92-98
2008
Homo sapiens
Avgeris, M.; Koutalellis, G.; Fragoulis, E.G.; Scorilas, A.
Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) inprostate cancer
Clin. Biochem.
41
1140-1149
2008
Homo sapiens
Hadjiconstantinou, M.; Neff, N.H.
Enhancing aromatic L-amino acid decarboxylase activity: implications for L-DOPA treatment in Parkinsons disease
CNS Neurosci. Ther.
14
340-351
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Ito, S.; Nakayama, T.; Ide, S.; Ito, Y.; Oguni, H.; Goto, Y.; Osawa, M.
Aromatic L-amino acid decarboxylase deficiency associated with epilepsy mimicking non-epileptic involuntary movements
Dev. Med. Child Neurol.
50
876-878
2008
Homo sapiens
Lee, H.F.; Tsai, C.R.; Chi, C.S.; Chang, T.M.; Lee, H.J.
Aromatic l-amino acid decarboxylase deficiency in Taiwan
Eur. J. Paediatr. Neurol.
13
135-140
2008
Homo sapiens
Traeger, C.; Vernby, A.; Kullman, A.; Ora, I.; Kogner, P.; Kagedal, B.
mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis
Int. J. Cancer
123
2849-2855
2008
Homo sapiens
Hofto, L.R.; Lee, C.E.; Cafiero, M.
The importance of aromatic-type interactions in serotonin synthesis: Protein-ligand interactionsin tryptophan hydroxylase and aromatic amino acid decarboxylase
J. Comput. Chem.
30
1111-1115
2008
Homo sapiens
Manegold, C.; Hoffmann, G.F.; Degen, I.; Ikonomidou, H.; Knust, A.; Laass, M.W.; Pritsch, M.; Wilichowski, E.; Hoerster, F.
Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up
J. Inherit. Metab. Dis.
32
371-380
2009
Homo sapiens
Cunningham, J.; Pivirotto, P.; Bringas, J.; Suzuki, B.; Vijay, S.; Sanftner, L.; Kitamura, M.; Chan, C.; Bankiewicz, K.S.
Biodistribution of adeno-associated virus type-2 in nonhuman primates after convection-enhanced delivery to brain
Mol. Ther.
16
1267-1275
2008
Homo sapiens
Eberling, J.L.; Jagust, W.J.; Christine, C.W.; Starr, P.; Larson, P.; Bankiewicz, K.S.; Aminoff, M.J.
Results from a phase I safety trial of hAADC gene therapy for Parkinson disease
Neurology
70
1980-1983
2008
Homo sapiens
Bertoldi, M.; Voltattorni, C.B.
Multiple roles of the active site lysine of Dopa decarboxylase
Arch. Biochem. Biophys.
488
130-139
2009
Homo sapiens
Ide, S.; Sasaki, M.; Kato, M.; Shiihara, T.; Kinoshita, S.; Takahashi, J.Y.; Goto, Y.
Abnormal glucose metabolism in aromatic L-amino acid decarboxylase deficiency
Brain Dev.
32
506-510
2010
Homo sapiens
Kitahama, K.; Ikemoto, K.; Jouvet, A.; Araneda, S.; Nagatsu, I.; Raynaud, B.; Nishimura, A.; Nishi, K.; Niwa, S.
Aromatic L-amino acid decarboxylase-immunoreactive structures in human midbrain, pons, and medulla
J. Chem. Neuroanat.
38
130-140
2009
Homo sapiens
Allen, G.F.; Neergheen, V.; Oppenheim, M.; Fitzgerald, J.C.; Footitt, E.; Hyland, K.; Clayton, P.T.; Land, J.M.; Heales, S.J.
Pyridoxal 5-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states
J. Neurochem.
114
87-96
2010
Homo sapiens
Kokkinou, I.; Fragoulis, E.G.; Vassilacopoulou, D.
The U937 macrophage cell line expresses enzymatically active L-Dopa decarboxylase
J. Neuroimmunol.
216
51-58
2009
Homo sapiens
Allen, G.F.; Land, J.M.; Heales, S.J.
A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency
Mol. Genet. Metab.
97
6-14
2009
Homo sapiens
Giegling, I.; Moreno-De-Luca, D.; Calati, R.; Hartmann, A.M.; Moeller, H.J.; De Ronchi, D.; Rujescu, D.; Serretti, A.
Tyrosine hydroxylase and DOPA decarboxylase gene variants in personality traits
Neuropsychobiology
59
23-27
2009
Homo sapiens
Kontos, C.K.; Papadopoulos, I.N.; Fragoulis, E.G.; Scorilas, A.
Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma
Br. J. Cancer
102
1384-1390
2010
Homo sapiens
Chalatsa, I.; Nikolouzou, E.; Fragoulis, E.G.; Vassilacopoulou, D.
L-Dopa decarboxylase expression profile in human cancer cells
Mol. Biol. Rep.
38
1005-1011
2011
Homo sapiens
Chalatsa, I.; Fragoulis, E.G.; Vassilacopoulou, D.
Release of membrane-associated L-dopa decarboxylase from human cells
Neurochem. Res.
36
1426-1434
2011
Homo sapiens
Ren, J.; Zhang, Y.; Jin, H.; Yu, J.; Zhou, Y.; Wu, F.; Zhang, W.
Novel inhibitors of human DOPA decarboxylase extracted from Euonymus glabra Roxb.
ACS Chem. Biol.
9
897-903
2014
Homo sapiens
Montioli, R.; Cellini, B.; Dindo, M.; Oppici, E.; Voltattorni, C.
Interaction of human Dopa decarboxylase with L-dopa: Spectroscopic and kinetic studies as a function of pH
BioMed Res. Int.
2013
161456
2013
Homo sapiens
Hoefig, C.S.; Renko, K.; Piehl, S.; Scanlan, T.S.; Bertoldi, M.; Opladen, T.; Hoffmann, G.F.; Klein, J.; Blankenstein, O.; Schweizer, U.; Koehrle, J.
Does the aromatic L-amino acid decarboxylase contribute to thyronamine biosynthesis?
Mol. Cell. Endocrinol.
349
195-201
2012
Homo sapiens (P20711), Homo sapiens
Daidone, F.; Montioli, R.; Paiardini, A.; Cellini, B.; Macchiarulo, A.; Giardina, G.; Bossa, F.; Borri Voltattorni, C.
Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors
PLoS ONE
7
e31610
2012
Homo sapiens
Giardina, G.; Montioli, R.; Gianni, S.; Cellini, B.; Paiardini, A.; Voltattorni, C.B.; Cutruzzola, F.
Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases
Proc. Natl. Acad. Sci. USA
108
20514-20519
2011
Homo sapiens (P20711), Homo sapiens
Bertoldi, M.
Mammalian dopa decarboxylase structure, catalytic activity and inhibition
Arch. Biochem. Biophys.
546
1-7
2014
Rattus norvegicus (P14173), Homo sapiens (P20711), Sus scrofa (P80041)
Portaro, S.; Gugliandolo, A.; Scionti, D.; Cammaroto, S.; Morabito, R.; Leonardi, S.; Fraggetta, F.; Bramanti, P.; Mazzon, E.
When dysphoria is not a primary mental state a case report of the role of the aromatic L-aminoacid decarboxylase
Medicine (Baltimore)
97
e10953
2018
Homo sapiens
Sanchez-Jimenez, F.; Pino-Angeles, A.; Rodriguez-Lopez, R.; Morales, M.; Urdiales, J.L.
Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks biomedical implications
Pharmacol. Res.
114
90-102
2016
Homo sapiens (P20711), Homo sapiens
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