Information on EC 4.1.1.28 - aromatic-L-amino-acid decarboxylase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC4.1.1.28
Word Map on EC 4.1.1.28
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Homo sapiens


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
4.1.1.28
-
RECOMMENDED NAME
GeneOntology No.
aromatic-L-amino-acid decarboxylase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
(S)-reticuline biosynthesis I
-
-
betaxanthin biosynthesis
-
-
betaxanthin biosynthesis (via dopamine)
-
-
catecholamine biosynthesis
-
-
serotonin and melatonin biosynthesis
-
-
catecholamine biosynthesis
-
-
tryptophan metabolism
-
-
Tyrosine metabolism
-
-
Phenylalanine metabolism
-
-
Tryptophan metabolism
-
-
Isoquinoline alkaloid biosynthesis
-
-
Betalain biosynthesis
-
-
Metabolic pathways
-
-
Biosynthesis of secondary metabolites
-
-
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 hide
9042-64-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,4-Dihydroxyphenylalanine
3-Hydroxytyramine + CO2
show the reaction diagram
-
-
-
-
-
3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
5-hydroxy-L-tryptophan
5-hydroxytryptamine + CO2
show the reaction diagram
-
-
?
5-hydroxy-L-tryptophan
serotonin + CO2
show the reaction diagram
-
-
-
-
?
5-hydroxytryptophan
5-hydroxytryptamine + CO2
show the reaction diagram
-
-
serotonin
-
-
5-Hydroxytryptophan
Serotonin + CO2
show the reaction diagram
carbidopa
?
show the reaction diagram
-
interaction of carbidopa with the Phe103 residue of the enzyme, the residue forms a displaced sandwich-type sigma-complex with carbidopa
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
L-5-hydroxytryptophan
serotonin + CO2
show the reaction diagram
-
-
-
-
?
L-Dopa
dopamine + CO2
show the reaction diagram
L-phenylalanine
2-phenylethylamine + CO2
show the reaction diagram
-
-
-
-
?
L-Trp
Tryptamine + CO2
show the reaction diagram
-
-
-
-
?
L-tryptophan
tryptamine + CO2
show the reaction diagram
m-tyrosine
m-tyramine + CO2
show the reaction diagram
-
-
-
-
?
p-tyrosine
p-tyramine + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
5-hydroxytryptophan
5-hydroxytryptamine + CO2
show the reaction diagram
-
-
serotonin
-
-
5-Hydroxytryptophan
Serotonin + CO2
show the reaction diagram
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
L-Dopa
dopamine + CO2
show the reaction diagram
L-phenylalanine
2-phenylethylamine + CO2
show the reaction diagram
-
-
-
-
?
L-Trp
Tryptamine + CO2
show the reaction diagram
-
-
-
-
?
L-tryptophan
tryptamine + CO2
show the reaction diagram
m-tyrosine
m-tyramine + CO2
show the reaction diagram
-
-
-
-
?
p-tyrosine
p-tyramine + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Al3+
-
activates
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
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
5-hydroxytryptophan
-
-
Benserazide
-
competitive inhibitor of L-Dopa, but a non-competitive inhibitor of 5-hydroxytryptophan
carbidopa
Cu2+
-
-
dopamine
L-Dopa
NSD-1015
-
-
Zn2+
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
haloperidol
-
enhanced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor antagonist
light
-
increases AAAD activity in retina
-
mecamylamine
-
drug acting on cholinerg receptor type enhances AAAD activity
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.074 - 0.62
3,4-dihydroxyphenylalanine
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 37C
0.016
5-hydroxytryptophan
-
-
0.00083 - 0.0505
dopamine
0.047 - 0.053
L-5-hydroxytryptophan
0.000095 - 4.27
L-Dopa
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7 - 2.48
dopamine
0.07 - 0.188
L-Dopa
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0044
2-[[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)sulfonyl]amino]-N-phenylbenzamide
-
pH 7.4, 25C
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, 25C
0.0018
4-[(E)-[(3-phenyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl]benzene-1,2-diol
-
pH 7.4, 25C
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, 25C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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, 25C
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, 25C
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, 25C
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, 25C
0.33
dopamine
Homo sapiens
-
inhibits the conversion of 5-hydroxy-L-tryptophan
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00003
-
enzyme from HTB-14 cells, at 37C, pH not specified in the publication
0.00006
-
enzyme from HeLa cells, at 37C, pH not specified in the publication
0.01037
-
solubilized enzyme, at pH 5.0 and 37C, using L-Dopa as substrate
3.67
-
activity in peripheral leukocytes, determined by radiochemical method at 37C
10
-
positive controls (embryonic K293 cells)
10.03
-
enzyme from SH-SY5Y cells, at 37C, pH not specified in the publication
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
-
3,4-dihydroxyphenylalanine as substrate
7 - 8.4
-
5-hydroxytryptophan as substrate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
rom the posterior iliac crest of children with neuroblastoma
Manually annotated by BRENDA team
-
high DDC mRNA expression levels are found in well-differentiated and Dukes' stage A and B tumors
Manually annotated by BRENDA team
-
neural and non-neural type DDC
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
expression of neural-type and non-neural DDC isoform
Manually annotated by BRENDA team
-
peripheral; peripheral leukocyte
Manually annotated by BRENDA team
-
IMR 32, CHP-212, SH-SY5Y, SK-N-SH, SK-N-FI, SK-N-AS, SK-N-BE(2) and SK-N-DZ
Manually annotated by BRENDA team
-
striatal neurons
Manually annotated by BRENDA team
-
prostate cancer
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
total RNA is isolated from tissue specimens from benign prostate hyperplasia and prostate cancer patients
Manually annotated by BRENDA team
additional information
-
tissue specificity is proposed to be directed by both alternative promoter usage and alternative splicing
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
-
-
Manually annotated by BRENDA team
additional information
-
a significant number of proteins exist in membrane-associated and soluble forms
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
-
alternative DDC isoform, SDS-PAGE
100000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 50000, SDS-PAGE
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
plays a role in the activation of the enzyme in vivo
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
apoenzyme, to 2.9 A resolution. The apoenzye 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
-
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
Discovery C18 column chromatography, gel filtration
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA, alternative mRNA splice variants, neuronal and nonneuronal
-
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
-
expressed in Escherichia coli
-
expressed in Escherichia coli XL-1 Blue cells
-
expressed in LNCaP cells
-
expression in COS cells
-
expression in Escherichia coli
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
-
mutant enzyme K303A is expressed in Escherichia coli SVS370 cells
-
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
4-deoxypyridoxine reduces aromatic L-amino acid decarboxylase mRNA levels
-
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
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
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.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
development o a high-throughput assay for testing of inhibitors
drug development
-
Parkinson disease, gene therapy, initiation of a phase I safety trial
medicine
pharmacology
biosynthesis of pharmaceutically important monoterpenoid indole alkaloids