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Information on EC 4.1.1.28 - aromatic-L-amino-acid decarboxylase
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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
-
monoamine
- parkinsonism
- striatum
- catecholamine
-
neurotransmitter
- carbidopa
- levodopa
- noradrenaline
- norepinephrine
- benserazide
- 5-hydroxytryptamine
-
dopac
-
substantia
- catechol-o-methyltransferase
- tryptamine
- roseus
-
serotonergic
-
nigrostriatal
- catharanthus
- dyskinesia
- beta-hydroxylase
-
catecholaminergic
-
5-hydroxyindoleacetic
-
3,4-dihydroxyphenylacetic
-
homovanillic
-
l-dopa-induced
- pargyline
- strictosidine
- l-dihydroxyphenylalanine
- apomorphine
-
5-hiaa
- dopamine-beta-hydroxylase
-
monoaminergic
- alpha-methyl-p-tyrosine
-
raphe
- 3-methoxytyramine
-
autoreceptors
- gamma-butyrolactone
-
non-dopaminergic
-
dihydroxyphenylacetic
-
catecholamine-synthesizing
-
tuberoinfundibular
- phenylethanolamine
- entacapone
-
antiparkinsonian
- quinpirole
- pharmacology
- medicine
-
6-hydroxydopamine-lesioned
- synthesis
- drug development
- analysis
- tolcapone
The enzyme appears in viruses and cellular organisms
Synonyms
3,4-dihydroxyphenylalanine carboxylase, 3,4-Dihydroxyphenylalanine decarboxylase, 5-Hydroxy-L-tryptophan decarboxylase, 5-Hydroxytryptophan decarboxylase, 5-hydroxytryptophan hydroxylase, 5HTP decarboxylase, AAAC, AAAD, AACD, AADC, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3,4-Dihydroxyphenylalanine decarboxylase
5-Hydroxy-L-tryptophan decarboxylase
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-
-
-
5-Hydroxytryptophan decarboxylase
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-
-
-
5-hydroxytryptophan hydroxylase
AAAD
AADC
Aromatic amino acid decarboxylase
Aromatic L-amino acid decarboxylase
DDC
Decarboxylase, aromatic amino acid
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-
-
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Dihydroxyphenylalanine-5-hydroxytryptophan decarboxylase
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-
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DOPA DC
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-
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DOPA decarboxylase
DOPA-5-hydroxytryptophan decarboxylase
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-
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EC 4.1.1.26
EC 4.1.1.27
Hydroxytryptophan decarboxylase
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-
-
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L-3,4-Dihydroxyphenylalanine decarboxylase
L-5-Hydroxytryptophan decarboxylase
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-
-
-
L-amino acid decarboxylase
L-Aromatic amino acid decarboxylase
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-
-
-
L-DOPA decarboxylase
L-Tryptophan decarboxylase
PP_2552
TDC
Tryptophan decarboxylase
TYDC
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-
-
-
Tyrosine/Dopa decarboxylase
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-
-
-
3,4-Dihydroxyphenylalanine decarboxylase
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-
-
-
AADC
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-
-
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AADC
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Aromatic amino acid decarboxylase
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-
-
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Aromatic L-amino acid decarboxylase
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-
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Aromatic L-amino acid decarboxylase
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Aromatic L-amino acid decarboxylase
Micrococcus percitreus AJ 1065
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-
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Aromatic L-amino acid decarboxylase
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DDC
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-
-
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DDC
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DDC
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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
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DOPA decarboxylase
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EC 4.1.1.26
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-
formerly
-
EC 4.1.1.27
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formerly
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L-3,4-Dihydroxyphenylalanine decarboxylase
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-
-
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L-DOPA decarboxylase
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-
-
-
L-DOPA decarboxylase
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L-Tryptophan decarboxylase
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Tryptophan decarboxylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-hydroxy-L-tryptophan = 5-hydroxytryptamine + CO2
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-
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L-dopa = dopamine + CO2
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L-dopa = dopamine + CO2
investigation of the mechanism by using the absorption spectrum of the bound coenzyme as an indicator of events
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L-dopa = dopamine + CO2
decarboxylation reaction mechanism, overview. Reaction via a Michaelis complex and a N4'-protonated external aldimine, respectively, the substrate L-dopa preferentially binds unprotonated to the N4'-protonated internal Schiff base
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
Pictet-Spengler cyclization
transamination
decarboxylation
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-
-
-
decarboxylation
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Pictet-Spengler cyclization
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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
transamination
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half-transamination of D-aromatic amino acid and aromatic amines under anaerobic conditions catalyzed by DDC
transamination
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half-transamination of D-aromatic amino acid and aromatic amines under anaerobic conditions catalyzed by DDC
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PATHWAY SOURCE
PATHWAYS
KEGG
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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.
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CAS REGISTRY NUMBER
COMMENTARY
9042-64-2
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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
2-fluoro-L-(3,4-dihydroxyphenyl)alanine
4-(2-aminoethyl)-3-fluorobenzene-1,2-diol + CO2
-
-
-
?
3,4-dihydroxyphenylalanine
4-(2-aminoethyl)benzene-1,2-diol + CO2
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-
-
?
3,4-dihydroxyphenylalanine
? + CO2
-
regulation of the ganglionic dopamine level
-
?
3,5-dibromo-DL-tyrosine
?
Micrococcus percitreus
-
72% activity compared to L-tryptophan
-
-
?
5-fluoro-DL-tryptophan
?
Micrococcus percitreus
-
75% activity compared to L-tryptophan
-
-
?
5-fluoro-L-(3,4-dihydroxyphenyl)alanine
5-(2-aminoethyl)-3-fluorobenzene-1,2-diol + CO2
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-
-
?
5-hydroxy-L-tryptophan
?
Micrococcus percitreus
-
24% activity compared to L-tryptophan
-
-
?
5-hydroxytryptamine + O2
5-hydroxyindolacetaldehyde + NH3
-
side reaction, decarboxylation-dependent transamination
-
?
5-methyl-DL-tryptophan
?
Micrococcus percitreus
-
17% activity compared to L-tryptophan
-
-
?
6-fluoro-L-(3,4-dihydroxyphenyl)alanine
4-(2-aminoethyl)-5-fluorobenzene-1,2-diol + CO2
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-
-
?
6-fluoro-threo-(3,4-dihydroxyphenyl)serine
4-(2-aminoethyl)-5-fluorobenzene-1,2-diol + CO2
-
-
-
?
alpha-methyl-DL-phenylalanine
?
Micrococcus percitreus
-
2% activity compared to L-tryptophan
-
-
?
alpha-methyl-DL-tyrosine
?
Micrococcus percitreus
-
1% activity compared to L-tryptophan
-
-
?
alpha-methyl-dopamine + O2
3,4-dihydroxyphenylacetone + NH3
-
side reaction, decarboxylation-dependent transamination
-
?
carbidopa
?
-
interaction of carbidopa with the Phe103 residue of the enzyme, the residue forms a displaced sandwich-type sigma-complex with carbidopa
-
-
?
L-(3,4-dihydroxyphenyl)alanine
4-(2-aminoethyl)benzene-1,2-diol + CO2
-
-
-
?
L-2,4-dihydroxyphenylalanine
?
Micrococcus percitreus
-
75% activity compared to L-tryptophan
-
-
?
L-kynurenine
3-amino-1-(2-aminophenyl)propan-1-one + CO2
Micrococcus percitreus
-
15% of the activity with L-Trp
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-
-
L-threo-(3,4-dihydroxyphenyl)serine
4-[(2-hydroxyethyl)amino]benzene-1,2-diol + CO2
-
-
-
?
3,4-Dihydroxy-L-phenylalanine
?
Micrococcus percitreus
-
10% activity compared to L-tryptophan
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-
?
3,4-Dihydroxy-L-phenylalanine
?
Micrococcus percitreus AJ 1065
-
10% activity compared to L-tryptophan
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-
?
3,4-Dihydroxyphenylalanine
3-Hydroxytyramine + CO2
-
little stereospecificity between D-3,4-dihydroxyphenylalanine and L-3,4-dihydroxyphenylalanine
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3,4-Dihydroxyphenylalanine
3-Hydroxytyramine + CO2
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-
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3,4-Dihydroxyphenylalanine
Dopamine + CO2
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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
-
-
?
3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-DOPA, substrate exerts apoptotic cytotoxicity towards PC12 cells at a concentration of 0.1-0.2 mM for 24-48 h
major amine neurotransmitter
-
?
3-Hydroxy-DL-kynurenine
?
Micrococcus percitreus
-
8% activity compared to L-tryptophan
-
-
?
3-Hydroxy-DL-kynurenine
?
Micrococcus percitreus AJ 1065
-
8% activity compared to L-tryptophan
-
-
?
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
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-
?
5-Hydroxytryptophan
Serotonin + CO2
Micrococcus percitreus
-
24% of the activity with L-Trp
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-
-
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
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L-dopa, levodopa, AADC constitutes the last enzymatic step in the biosynthesis of dopamine
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
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L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
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-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
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L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
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DOPA, plays a role in the neuromodulation of behavior
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
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-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
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the renal dopaminergic system is highly dynamic and the basic mechanisms for the regulation of this system mainly depends on the availability of L-dopa, its fast decarboxylation into dopamine, precise cell outward amine transfer mechanisms, dopamine interaction with specific receptor and accurate intracellular signal transduction
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-
?
L-Dopa
dopamine + CO2
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dopamine can serve as the catecholamine substrate for melanin production
-
?
L-Dopa
dopamine + CO2
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dopamine has a neural role and is metabolized to produce melanin and sclerotin in epidermal tissues
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?
L-Dopa
dopamine + CO2
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691469, 691846, 692661, 693374, 701921, 702954, 704803, 705265, 705269, 705756, 705914, 714634, 716172, 716342
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?
L-Dopa
dopamine + CO2
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enzyme is central in the synthesis of biogenic monoamine neurotransmitters, these include serotonin as well as the catecholamines dopamine and norepinephrine (noradrenaline)
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-
?
L-Dopa
dopamine + CO2
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second enzyme in the catecholamine biosynthetic pathway that catalyzes the synthesis of important neurotransmitters
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-
?
L-Dopa
dopamine + CO2
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substrate ionization is related to the catalytic event
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-
?
L-Dopa
dopamine + CO2
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clozapine modulates AAAD activity in striatum and enhances exogenous L-DOPA decarboxylation in intact mice and mice lesioned with1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Kinetic analysis of AAAD at 1 h showed an increase in the apparent Vmax for both the substrate L-DOPA and the cofactor pyridoxal-5'-phosphate with no changes for Km. Dopamine D4 and 5-HT2A and 5-HT1A antagonists also increase AAAD activity in striatum
-
-
?
L-Dopa
dopamine + CO2
biosynthesis of catecholamine neurotransmitters and serotonin
-
-
?
L-Phe
phenylethylamine + CO2
Micrococcus percitreus
-
m-DL-Tyr, 17% of the activity with L-Trp
-
-
-
L-Phe
phenylethylamine + CO2
Micrococcus percitreus
-
o-DL-Tyr, 17% of the activity with L-Trp
-
-
-
L-Phe
phenylethylamine + CO2
Micrococcus percitreus
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L-Tyr, 120% of the activity with L-Trp
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L-phenylalanine
?
Micrococcus percitreus AJ 1065
-
87% activity compared to L-tryptophan
-
-
?
L-tryptophan
tryptamine + CO2
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
catalyzes an early step of the terpenoid indole alkaloid biosynthetic pathway
-
?
L-tryptophan
tryptamine + CO2
-
enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathway, second step enzyme for monoamine synthesis
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
N-methyl-L-dopa
N-methyldopamine + CO2
-
in addition, enzyme catalyses the decarboxylation-dependent oxidative deamination of alpha-methyl-dopa, but the oxidative reaction is considerably slower than the decarboxylation reaction
-
?
N-methyl-L-dopa
N-methyldopamine + CO2
-
in addition, enzyme catalyses the decarboxylation-dependent oxidative deamination of alpha-methyl-dopa, but the oxidative reaction is considerably slower than the decarboxylation reaction
-
?
o-fluorophenylalanine
o-fluorophenylethylamine + CO2
-
-
-
?
additional information
?
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-
enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
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-
additional information
?
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enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
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additional information
?
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enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
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additional information
?
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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
?
-
exclusive substrate specificity for L-amino acids with either indole or phenol side chains, but not both, L-tyrosine, L-phenylalanine and L-Dopa are not accepted as substrates
-
?
additional information
?
-
exclusive substrate specificity for L-amino acids with either indole or phenol side chains, but not both, L-tyrosine, L-phenylalanine and L-Dopa are not accepted as substrates
-
?
additional information
?
-
-
no significant activity towards aliphatic amino acids
-
-
-
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
?
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-
Ddc activities are key regulatory components for haemocyte aggregation and melanization in the presence of bacteria
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-
additional information
?
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Ddc activities are key regulatory components for haemocyte aggregation and melanization in the presence of bacteria
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-
additional information
?
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Ddc is involved in wound healing, parasite defense, cuticle hardening, melanization and in the behavior of insects
-
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-
additional information
?
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Ddc is involved in wound healing, parasite defense, cuticle hardening, melanization and in the behavior of insects
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-
additional information
?
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exclusive substrate specificity for L-amino acids with either indole or phenol side chains, but not both, L-tyrosine, L-phenylalanine and L-Dopa are not accepted as substrates
-
?
additional information
?
-
-
exclusive substrate specificity for L-amino acids with either indole or phenol side chains, but not both, L-tyrosine, L-phenylalanine and L-Dopa are not accepted as substrates
-
?
additional information
?
-
-
DDC activity is required in the epidermis for the synthesis of dopamine that is metabolized to produce reactive quinones that exert killing effects on invading bacteria
-
-
-
additional information
?
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DDC plays a role in the Drosophila innate immune response in larvae and adults
-
-
-
additional information
?
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dopa decarboxylase plays an essential role in wound healing in the Drosophila embryo
-
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-
additional information
?
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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
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additional information
?
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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
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-
additional information
?
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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
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additional information
?
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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
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additional information
?
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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
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additional information
?
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L-dopa decarboxylase is a pyridoxal 5'-phosphate-dependent enzyme involved in many malignancies
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-
additional information
?
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Mutations that decrease substrate binding can result in a decrease in serotonin production and thus can lead to depression and related disorders
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additional information
?
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regulating factor of the proliferation and differentiation of different leukocyte subtypes
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-
additional information
?
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tyrosine hydroxylase mRNA and DDC mRNA in plasma of children with neuroblastoma are highly correlated
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additional information
?
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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
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-
additional information
?
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normal movement and behavior do not depend on complete recovery of enzyme function (after suicide inhibition), but likely on pre-synaptic and post-synaptic compensatory mechanisms
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-
-
additional information
?
-
Micrococcus percitreus
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no activity with 4-nitro-DL-phenylalanine, 3,5-dinitro-DL-tyrosine, 2,4,4-trihydroxyphenyl-L-alanine, alpha-methyl-3,4-dihydroxy-phenyl-L-alanine, 2-phenyl-DL-serine, 2-thiazole-DL-alanine, and L-histidine
-
-
-
additional information
?
-
Micrococcus percitreus AJ 1065
-
no activity with 4-nitro-DL-phenylalanine, 3,5-dinitro-DL-tyrosine, 2,4,4-trihydroxyphenyl-L-alanine, alpha-methyl-3,4-dihydroxy-phenyl-L-alanine, 2-phenyl-DL-serine, 2-thiazole-DL-alanine, and L-histidine
-
-
-
additional information
?
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DDC is involved in the synthesis of dopamine, serotonin and acts as an androgen receptor co-regulator protein
-
-
-
additional information
?
-
the imprinting and developmental regulation of Ddc_exon1a expression in the heart suggests fundamental roles in cardiogenesis and cardiac function
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-
additional information
?
-
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the key step in the formation of the aromatic amines dopamine, epinephrine and norepinephrine is catalyzed by a single enzyme
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-
additional information
?
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-
no enzyme activity detected with D-phenylalanine, L-5-hydroxytryptophan or L-histidine
-
?
additional information
?
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no enzyme activity detected with D-phenylalanine, L-5-hydroxytryptophan or L-histidine
-
?
additional information
?
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enzyme is essentially inactive towards other aromatic amino acids such as 5-hydroxy-L-tryptophan, Lphenylalanine, L-tryptophan and L-tyrosine
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-
-
additional information
?
-
enzyme is essentially inactive towards other aromatic amino acids such as 5-hydroxy-L-tryptophan, Lphenylalanine, L-tryptophan and L-tyrosine
-
-
-
additional information
?
-
enzyme is essentially inactive towards other aromatic amino acids such as 5-hydroxy-L-tryptophan, Lphenylalanine, L-tryptophan and L-tyrosine
-
-
-
additional information
?
-
-
key enzyme in the production of biogenic amines
-
-
-
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
?
-
-
DOPA cyclohexyl ester is an antagonist of DOPA
-
-
-
additional information
?
-
-
exclusive substrate specificity for L-amino acids with either indole or phenol side chains, but not both, L-tyrosine, L-phenylalanine and L-Dopa are not accepted as substrates
-
?
additional information
?
-
-
exhibits half-transaminase activity toward D-aromatic amino acids and oxidative deaminase activity toward aromatic amines
-
?
additional information
?
-
-
catalyzes the decarboxylation of aromatic amino acids into their corresponding amines
-
-
-
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
?
-
-
the pig DDC is able to catalyze oxidative deamination of aromatic amines, cf. EC 4.3.1., and the generated carbonyl compounds act as suicide or mechanism-based inhibitors of the enzyme, catalytic mechanism with formation of a ketimine and superoxide as reaction intermediates, overview. The stoichiometry of dioxygen consumed with respect to carbonyl compound and ammonia formed as well as amine oxidized is 1:2. Studies with an analogue of serotonin undergoing oxidative deamination with DDC, i.e. D-tryptophan methyl ester, shows the accumulation of the quinonoid intermediate of this reaction
-
-
-
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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
? + CO2
-
regulation of the ganglionic dopamine level
-
?
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
-
L-DOPA, substrate exerts apoptotic cytotoxicity towards PC12 cells at a concentration of 0.1-0.2 mM for 24-48 h
major amine neurotransmitter
-
?
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-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
DOPA, plays a role in the neuromodulation of behavior
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
L-dopa, levodopa, substrate alleviates the clinical symptoms of Parkinson disease
-
-
?
L-3,4-Dihydroxyphenylalanine
Dopamine + CO2
-
the renal dopaminergic system is highly dynamic and the basic mechanisms for the regulation of this system mainly depends on the availability of L-dopa, its fast decarboxylation into dopamine, precise cell outward amine transfer mechanisms, dopamine interaction with specific receptor and accurate intracellular signal transduction
-
-
?
L-Dopa
dopamine + CO2
-
dopamine can serve as the catecholamine substrate for melanin production
-
?
L-Dopa
dopamine + CO2
-
-
dopamine has a neural role and is metabolized to produce melanin and sclerotin in epidermal tissues
-
?
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
-
-
?
L-Dopa
dopamine + CO2
-
clozapine modulates AAAD activity in striatum and enhances exogenous L-DOPA decarboxylation in intact mice and mice lesioned with1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Kinetic analysis of AAAD at 1 h showed an increase in the apparent Vmax for both the substrate L-DOPA and the cofactor pyridoxal-5'-phosphate with no changes for Km. Dopamine D4 and 5-HT2A and 5-HT1A antagonists also increase AAAD activity in striatum
-
-
?
L-Dopa
dopamine + CO2
biosynthesis of catecholamine neurotransmitters and serotonin
-
-
?
L-tryptophan
tryptamine + CO2
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
L-tryptophan
tryptamine + CO2
-
catalyzes an early step of the terpenoid indole alkaloid biosynthetic pathway
-
?
L-tryptophan
tryptamine + CO2
-
enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathway, second step enzyme for monoamine synthesis
-
?
L-tryptophan
tryptamine + CO2
-
implicated in the biosynthesis of the plant hormone indole-3-acetic acid, also involved in the formation of the monoamine serotonin, and of simple alkaloids such as the beta-carbolines
-
?
additional information
?
-
-
enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
-
-
-
additional information
?
-
enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
-
-
-
additional information
?
-
enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
-
-
-
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
?
-
-
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
?
-
-
Ddc activities are key regulatory components for haemocyte aggregation and melanization in the presence of bacteria
-
-
-
additional information
?
-
Ddc activities are key regulatory components for haemocyte aggregation and melanization in the presence of bacteria
-
-
-
additional information
?
-
-
Ddc is involved in wound healing, parasite defense, cuticle hardening, melanization and in the behavior of insects
-
-
-
additional information
?
-
Ddc is involved in wound healing, parasite defense, cuticle hardening, melanization and in the behavior of insects
-
-
-
additional information
?
-
-
DDC activity is required in the epidermis for the synthesis of dopamine that is metabolized to produce reactive quinones that exert killing effects on invading bacteria
-
-
-
additional information
?
-
-
DDC plays a role in the Drosophila innate immune response in larvae and adults
-
-
-
additional information
?
-
-
dopa decarboxylase plays an essential role in wound healing in the Drosophila embryo
-
-
-
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
?
-
-
normal movement and behavior do not depend on complete recovery of enzyme function (after suicide inhibition), but likely on pre-synaptic and post-synaptic compensatory mechanisms
-
-
-
additional information
?
-
-
DDC is involved in the synthesis of dopamine, serotonin and acts as an androgen receptor co-regulator protein
-
-
-
additional information
?
-
the imprinting and developmental regulation of Ddc_exon1a expression in the heart suggests fundamental roles in cardiogenesis and cardiac function
-
-
-
additional information
?
-
-
the key step in the formation of the aromatic amines dopamine, epinephrine and norepinephrine is catalyzed by a single enzyme
-
-
-
additional information
?
-
-
key enzyme in the production of biogenic amines
-
-
-
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
?
-
-
DOPA cyclohexyl ester is an antagonist of DOPA
-
-
-
additional information
?
-
-
catalyzes the decarboxylation of aromatic amino acids into their corresponding amines
-
-
-
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
?
-
-
the pig DDC is able to catalyze oxidative deamination of aromatic amines, cf. EC 4.3.1., and the generated carbonyl compounds act as suicide or mechanism-based inhibitors of the enzyme, catalytic mechanism with formation of a ketimine and superoxide as reaction intermediates, overview. The stoichiometry of dioxygen consumed with respect to carbonyl compound and ammonia formed as well as amine oxidized is 1:2. Studies with an analogue of serotonin undergoing oxidative deamination with DDC, i.e. D-tryptophan methyl ester, shows the accumulation of the quinonoid intermediate of this reaction
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no absolute requirement for exogenous pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate
Micrococcus percitreus
-
covalently bound cofactor, 2 mol of pyridoxal 5'-phosphate bound per mol of enzyme
pyridoxal 5'-phosphate
-
0.0032-0.32 mM, enhances activity greater than 2fold
pyridoxal 5'-phosphate
-
addition of pyridoxal 5'-phosphate increases activity towards 3,4-dihydroxyphenylalanine, o-Tyr, m-Tyr, but not towards 5-hydroxytryptophan
pyridoxal 5'-phosphate
-
contains 1 mol of pyridoxal 5'-phosphate per mol of enzyme, nearly complete decarboxylation of L-3,4-dihydroxyphenylalanine in absence of added coenzyme, existence of at least 4 coenzyme-apoenzyme complexes, three of them are active
pyridoxal 5'-phosphate
-
5-hydroxytryptophan can be decarboxylated without exogenous addition of pyridoxal 5'-phosphate, addition of pyridoxal 5'-phosphate substantially increases enzyme activity. Excess of coenzyme, above 0.06 mM, induces inhibition in adrenals and liver but not in the central nervous system
pyridoxal 5'-phosphate
-
1 mol of pyridoxal 5'-phosphate is bound to the epsilon-amino group of a lysyl residue of the apoenzyme
pyridoxal 5'-phosphate
-
-
653356, 653443, 691469, 691846, 691888, 691987, 701921, 702954, 704803, 705269, 705914, 716172, 748845
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
-
one pyridoxal 5'-phosphate cofactor per dimer structure
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
pyridoxal 5'-phosphate
binding site is located at the amino acid position 313-334
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Na+
-
inverse correlation between DDC activity and sodium reabsorption in the kidney, confirming the hypothesis that dopamine inhibits sodium absorption
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
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-alpha-(fluoromethyl)tryptophan
-
the suicide substrate effectively inhibits TDC activity extracted from rice leaves infected by Bipolaris oryzae and the inhibition rate increases dependent on preincubation time
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
MPTP, after 7 days of treatment, AAAD activities are decreased by more than 50% in the mouse striatum
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'-hydroxybenzylhydrazine
-
NSD-1015, a central aromatic L-amino acid decarboxylase inhibitor
3,4-dihydroxyphenylalanine
-
inhibitory effect of 3,4-dihydroxyphenylalanine on the conversion of 5-hydroxy-L-tryptophan
3-(3,4-dihydroxyphenyl)-2-hydrazino-2-methyl propionic acid
-
carbiDOPA, addition of 10 microM inhibitor to reaction mixtures (Y332F mutant with L-dopa) in the presence or in the absence of catalase or superoxide dismutase, immediately stops the O2 consumption.
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
7-hydroxy-N,N-di-n-propyl-2-aminotetralin
-
reduced AAAD activity in the striatum by acute treatment with the D2-like receptor agonist
annexin 5
-
endogenous inhibitor, identified and purified from human placenta presented in the membrane function, shows 30.4% inhibition by incubation of the human placenta samples in the presence of 0.34 unit ddc from mouse kidney homogenate. The inhibitor exhibits an optimum activity at 50 mM NaCl, pH 6.5, is heat labile and is deactivated by boiling. After incubation of the placental homogenate with proteinase K, inhibitory activity is partially abolished, suggesting that a population of inhibitor molecules is embedded in the membrane.
-
benzerazide
Escherichia coli phagocytosis is blocked by benzerazide, revealing the involvement of Ddc activity in phagocytosis
bromocryptine
-
reduced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor agonist
Clorgyline
-
reduced AAAD activity in the striatum by acute treatment with the dopamine receptor indirect agonist
Fe2+
-
enzyme from pharate pupae, no effect on the enzyme from white prepupae
Pargyline
-
reduced AAAD activity in the striatum by acute treatment with the dopamine receptor indirect agonist
quinpirole
-
reduced AAAD activity in the striatum by chronic treatment with the D2-like receptor agonist
testosterone propionate
-
repetitive treatment of female mice with testosterone propionate for 2 weeks elicits a marked decrease in renal DCC activity
5-hydroxy-L-tryptophan
-
strong inhibitory effect of 5-hydroxy-L-tryptophan on the conversion of 3,4-dihydroxyphenylalanine
Al3+
-
enzyme from pharate pupae, no effect on the enzyme from white prepupae
Benserazide
-
competitive inhibitor of L-Dopa, but a non-competitive inhibitor of 5-hydroxytryptophan
Benserazide
-
levels of intracellular dopamine after L-DOPA treatment (0.02 and 0.1 mM) are significantly decreased by the AADC inhibitor benserazide (0.02 mM) for 6-24 h exposure prior to L-DOPA treatment in PC12 cells, the 230%-350% increases in dopamine levels by L-DOPA are reduced to 187%-284% by benserazide for 6 h
Benserazide
-
intrastriatal inhibition of the enzyme prevents the appearance of L-dopa-induced dyskinetic movements at the lesioned side
carbidopa
Escherichia coli phagocytosis is blocked by carbidopa, revealing the involvement of Ddc activity in phagocytosis
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
carbidopa
-
levels of intracellular dopamine after L-DOPA treatment (0.02 and 0.1 mM) are significantly decreased by the AADC inhibitor carbidopa (0.020 mM) for 6-24 h exposure prior to L-DOPA treatment in PC12 cells, the 230%-350% increases in dopamine levels by L-DOPA are reduced to 187%-284% by 153%-248% by carbidopa for 6 h
Cu2+
-
enzyme from pharate pupae, no effect on the enzyme from white prepupae
dopamine
-
the conversion of 5-hydroxy-L-tryptophan is strongly inhibited by dopamine
epigallocatechin-3-gallate
-
EGCG, the inhibitory effect is mediated by blocking the entrance to the catalytic site, therefore, preventing substrate binding
epigallocatechin-3-gallate
-
direct inhibitory effect on both histidine decarboxylase and DOPA decarboxylase. Modeling of binding to the enzymes. Epigallocatechin-3-gallate does not affect the quaternary structure of the enzyme and remains stable in the active site throughout the entire trajectory. After 700 ps of simulation, epigallocatechin-3-gallate moves deeper into the active site. While adopting this conformation, epigallocatechin-3-gallate actually fills the binding pocket and blocks its entrance pathway
Hg2+
-
enzyme from pharate pupae, no effect on the enzyme from white prepupae
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
L-Dopa
-
reduced AAAD activity in the striatum by acute and chronic treatment with the dopamine receptor indirect agonist
pyridoxal 5'-phosphate
-
inhibition at high concentrations, stimulation at lower concentration
pyridoxal 5'-phosphate
-
optimal concentration for pharate pupae enzyme: 0.02 mM; optimal concentration for the white pupae enzyme: 0.4 mM
serotonin
-
and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition
serotonin
-
and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition
serotonin
-
and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition
Zn2+
-
enzyme from pharate pupae,no effect on the enzyme from white prepupae
additional information
-
decrease of Escherichia coli phagocytosis in the presence of Ddc small interfering RNA of about 30%, compared with the controls; Escherichia coli phagocytosis is blocked by small interfering RNA for Ddc and antibodies against Ddc, revealing the involvement of Ddc activity in phagocytosis. Haemocyte-surface-associated Ddc is decreased by about 90% in haemocytes transfected with Ddc siRNA, compared to the control experiment; when haemocytes are pretreated with anti-Ddc instead of Ddc small interfering RNA before challenge with Escherichia coli, a greater decrease of Escherichia coli phagocytosis (about 60%) is observed, compared with the siRNA results (30%)
-
additional information
decrease of Escherichia coli phagocytosis in the presence of Ddc small interfering RNA of about 30%, compared with the controls; Escherichia coli phagocytosis is blocked by small interfering RNA for Ddc and antibodies against Ddc, revealing the involvement of Ddc activity in phagocytosis. Haemocyte-surface-associated Ddc is decreased by about 90% in haemocytes transfected with Ddc siRNA, compared to the control experiment; when haemocytes are pretreated with anti-Ddc instead of Ddc small interfering RNA before challenge with Escherichia coli, a greater decrease of Escherichia coli phagocytosis (about 60%) is observed, compared with the siRNA results (30%)
-
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
Micrococcus percitreus
-
not inhibited by D-tryptophan, kynuramine, octopamine, and 3-indoleacetate
-
additional information
-
in castrated male mice, DCC activity decreases in all parts of the small intestine, reaching values similar to those in females
-
additional information
-
not inhibited by L-alpha-fluoromethyltyrosine and L-alpha-fluoromethyl(3,4-dihydroxyphenyl)alanine
-
additional information
-
dopamine receptor activation decreases AAAD activity
-
additional information
-
L-3,4-dihydroxyphenylalanine (100 mg/kg) increases the striatal dopamine content but elicits no effect on locomotor activity in the presence of benserazide (50 mg/kg i.p.), a peripheral AADC inhibitor. L-3,4-dihydroxyphenylalanine increases the dopamine content in the presence of 3'-hydroxybenzylhydrazine to a maximal degree similar to that in the presence of benserazide. L-3,4-dihydroxyphenylalanine cyclohexyl ester is a suitable L-3,4-dihydroxyphenylalanine antagonist that would be available under in vivo experimental conditions.; L-3,4-dihydroxyphenylalanine cyclohexyl ester would antagonize the behavioral responses of conscious rats to L-3,4-dihydroxyphenylalanine in the presence of 3'-hydroxybenzylhydrazine. L-3,4-dihydroxyphenylalanine cyclohexyl ester elicits a dose-dependent partial antagonism against the increase in locomotor activity induced by L-3,4-dihydroxyphenylalanine. A low dose of L-3,4-dihydroxyphenylalanine cyclohexyl ester (10 mg/kg) elicits full antagonism against the potentiating effect of a non-effective dose of L-3,4-dihydroxyphenylalanine (20 mg/kg) on the increase in locomotor activity induced by a dopamine D2 agonist quinpirole (0.3 mg/kg s.c.). L-3,4-dihydroxyphenylalanine cyclohexyl ester elicits full antagonism against licking behavior induced by L-3,4-dihydroxyphenylalanine.
-
additional information
-
a decrease in urinary levels of dopamine and in renal AADC activity at 20 twenty-six weeks after renal mass ablation
-
additional information
-
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
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compounds acting via a suicide mechanism by alkylating the enzyme: alpha-chloromethyl and alpha-fluoromethyl derivatives of Dopa, a-vinylDopa and alpha-acetylenic Dopa. The phosphopyridoxyl aromatic amino acids Schiff base analogues and substrate analogues, like green tea polyphenols, also inhibit the enzyme
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
amantadine
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drug acting on glutamatergic receptor type enhances AAAD activity
budipine
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drug acting on glutamatergic receptor type enhances AAAD activity
cGMPdependent protein kinase Ialpha
phosphorylates and activates neuronal AAAD, maximal increase of activity is obtained at about 100-175 units during a 10 min incubation at 30°C
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clonidine
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drug acting on alpha adrenergic receptor type enhances AAAD activity
dextrometorphan
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drug acting on glutamatergic receptor type enhances AAAD activity
flupenthixol
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enhanced AAAD activity in the striatum by acute treatment with the D2-like receptor antagonist; enhances activity in rat striatum
forskolin
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intracerebroventricularly injection enhances the enzyme activity, a response, that can be blocked by selective inhibitors of protein kinase A
L-745,870
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enhanced AAAD activity in the striatum by acute treatment with the D2-like receptor antagonist
L-Dopa
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L-DOPA treatment (20-200 microM) increases the levels of dopamine by 226%-504% after 3-6 h of treatment and enhances the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase
memantine
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drug acting on glutamatergic receptor type enhances AAAD activity
phencyclidine
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drug acting on glutamatergic receptor type enhances AAAD activity
phorbol-12,13-myristic acid
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intracerebroventricularly injection enhances the enzyme activity, a response, that can be blocked by selective inhibitors of protein kinase A
pimozide
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enhanced AAAD activity in the striatum by acute treatment with the D2-like receptor antagonist
remoxipride
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enhanced AAAD activity in the striatum by acute treatment with the D2-like receptor antagonist
SCH 23390
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enhanced AAAD activity in the striatum by acute and chronic treatment with the D1-like receptor antagonist
SKF 38393
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enhanced AAAD activity in the striatum by chronic treatment with the D1-like receptor agonist
sulpiride
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enhanced AAAD activity by in the striatum by acute and chronic treatment with the D2-like receptor antagonist
clozapine
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enhanced AAAD activity in the striatum by acute treatment with the D2-like receptor antagonist
haloperidol
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enhanced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor antagonist
haloperidol
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enhanced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor antagonist
pyridoxal 5'-phosphate
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stimulated by addition of excess pyridoxal phosphate
spiperone
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enhanced AAAD activity in the striatum by acute and chronic treatment with the D2-like receptor antagonist
additional information
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A conserved AP-1 (JNK activated transcription factor complex) binding upstream of the DDC transcription start site is necessary to induce DDC transcription; aseptic wounding of larvae or adults does not lead to DDC transcriptional induction, unlike in embryos where DDC activity at the edge of the wound contributes to the formation of a melanin clot; Transcription of the dopa decarboxylase gene is induced in response to gram-negative and gram-positive septic injury, but not aseptic wounding. Ddc transcripts are detectible within 2 h and remain high for several hours following infection with either gram-negative (Escherichia coli) or gram-positive (Staphylococcus aureus) bacteria. Ddc transcription depends on a previously uncharacterized member of the p38 mitogen-activated protein kinase family, p38c
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additional information
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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.
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additional information
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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; the early activation of AAAD is followed by a late, longer lasting (hours) response, which is accompanied by an increase of mRNA and protein
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additional information
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high expression of DDC in blood and bone marrow corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome
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