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Enzyme Nomenclature
Information on EC 4.1.1.28 - aromatic-L-amino-acid decarboxylase
for references in articles please use BRENDA:EC4.1.1.28
Word Map on EC 4.1.1.28
- 4.1.1.28
- dopamine
- serotonin
-
dopaminergic
-
monoamine
- parkinsonism
- striatum
- catecholamine
-
neurotransmitter
-
decarboxylation
- noradrenaline
- carbidopa
- norepinephrine
-
dopac
- 5-hydroxytryptamine
- benserazide
- levodopa
-
5-hiaa
- dyskinesia
-
serotonergic
-
5-hydroxyindoleacetic
- apomorphine
- catharanthus
- roseus
- tryptamine
- catechol-o-methyltransferase
-
nigrostriatal
-
3,4-dihydroxyphenylacetic
-
homovanillic
- beta-hydroxylase
-
catecholaminergic
-
autoreceptors
- phenylethanolamine
- analysis
-
tuberoinfundibular
-
dihydroxyphenylacetic
-
l-dopa-induced
- l-dihydroxyphenylalanine
- medicine
- alpha-methyl-p-tyrosine
- quinpirole
- 3-methoxytyramine
- drug development
- pharmacology
- entacapone
-
monoaminergic
- gamma-butyrolactone
-
6-hydroxydopamine-lesioned
- synthesis
-
catecholamine-synthesizing
- strictosidine
- pargyline
-
non-dopaminergic
- dopamine-beta-hydroxylase
-
antiparkinsonian
- tolcapone
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
4.1.1.28
-
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RECOMMENDED NAME
GeneOntology No.
aromatic-L-amino-acid decarboxylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-hydroxy-L-tryptophan = 5-hydroxytryptamine + CO2
-
-
-
-
L-dopa = dopamine + CO2
investigation of the mechanism by using the absorption spectrum of the bound coenzyme as an indicator of events
-
L-dopa = dopamine + CO2
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
decarboxylation
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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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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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
filarial nematode, causative agent of heartworm disease in dogs and cats
-
-
isoform 1, descended from accession number AF063021; strain G3, the strain has the ability to melanize malaria parasites
UniProt
isoform 2, descended from accession number AF063021; strain G3, the strain has the ability to melanize malaria parasites
UniProt
-
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, 728566
-
-
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
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-
parental allele identity is inferred via a G3A single-nucleotide polymorphism between the Mus musculus C57BL6 (B6) and Mus musculus castaneus CAST/Ei (CAST) strains in exon 6 at nucleotide 645
UniProt
-
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
aromatic L-amino acid decarboxylase deficiency is characterized by oculogyric crises, paroxysmal dystonic attacks, and severe psychomotor retardation since early infancy
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
metabolism
-
the enzyme is involved in terpenoid indole alkaloid (TIA) biosynthetic pathway
metabolism
-
the enzyme is involved in biosynthesis of terpenoidindole alkaloids
physiological function
-
dopa decarboxylase is necessary for insect cuticular melanization
physiological function
DDC is involved in the Tribolium cuticle sclerotization and pigmentation pathway, and is a candidate for the gene that is mutated in black
physiological function
neuronal AAAD plays a role in the biosynthesis of catecholamines, indoleamines and trace amines in the nervous system
physiological function
-
DDC modulates the immune responses such as hemocytes encapsulation as well as the reactive oxygen species level through its catalytic activity, functioning as an indispensable immunomodulating enzyme in the neuroendocrine-immune regulatory network of mollusk
physiological function
transgenic hairy root lines produce inceased amounts of tryptamine, but are unable to produce mitragynine
physiological function
-
the tyrosine or phenylalanine residue in the catalytic loop region could serve as a signature residue to reliably distinguish plant arylalkylamine and aldehyde synthesizing aromatic amino acid decarboxylases
physiological function
-
the tyrosine or phenylalanine residue in the catalytic loop region could serve as a signature residue to reliably distinguish plant arylalkylamine and aldehyde synthesizing aromatic amino acid decarboxylases
physiological function
-
RNAi-induced dopa decarboxylase expression obviously declines in the silkworm larvae, and the pupae show no pupation or incomplete pupation
physiological function
inhibition of dopa dearboxylase by inhibitor NSD-1015 or anti-sense morpholino oligonucleotides reduces brain volume and body length. Oligonucleotide-treated emryos display brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons as well as seizure-like activity in a dose-dependent manner. Treated embroys have less sensitive touch response and impaired swimming activity that can be rescued by injection of plasmids carrying the dopa decarboxylase gene. In addition, eye movement is significantly impaired in treated embryos
physiological function
during bacillamide C biosynthesis, the decarboxylation of L-tryptophan to tryptamine is likely conducted first under aromatic L-amino acid decarboxylase catalysis, followed by the amidation of tryptamine with the carboxylic product of non-ribosomal peptide synthetases gene cluster
physiological function
-
during bacillamide C biosynthesis, the decarboxylation of L-tryptophan to tryptamine is likely conducted first under aromatic L-amino acid decarboxylase catalysis, followed by the amidation of tryptamine with the carboxylic product of non-ribosomal peptide synthetases gene cluster
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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
2,4-dihydroxyphenyl-L-alanine
?
Micrococcus percitreus
-
75% activity compared to L-tryptophan
-
-
?
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
-
-
-
?
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
-
-
-
?
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
-
-
-
?
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-kynurenine
3-amino-1-(2-aminophenyl)propan-1-one + CO2
Micrococcus percitreus
-
15% of the activity with L-Trp
-
-
-
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
-
-
?
3,4-Dihydroxy-L-phenylalanine
?
Micrococcus percitreus AJ 1065
-
10% activity compared to L-tryptophan
-
-
?
3,4-Dihydroxyphenylalanine
3-Hydroxytyramine + CO2
-
little stereospecificity between D-3,4-dihydroxyphenylalanine and L-3,4-dihydroxyphenylalanine
-
-
3,4-Dihydroxyphenylalanine
3-Hydroxytyramine + CO2
-
-
-
-
-
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
-
-
?
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
-
-
?
5-Hydroxytryptophan
Serotonin + CO2
Micrococcus percitreus
-
24% of the activity with L-Trp
-
-
-
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
-
-
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
-
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
-
L-Tyr, 120% of the activity with L-Trp
-
-
-
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
?
-
-
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
?
-
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
?
-
-
Ddc activities are key regulatory components for haemocyte aggregation and melanization in the presence of bacteria
-
-
-
additional information
?
-
O45216;
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
?
-
O45216;
Ddc is involved in wound healing, parasite defense, cuticle hardening, melanization and in the behavior of insects
-
-
-
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
?
-
-
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
?
-
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
?
-
-
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
?
-
Micrococcus percitreus
-
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
?
-
-
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
?
-
-
no enzyme activity detected with D-phenylalanine, L-5-hydroxytryptophan or L-histidine
-
?
additional information
?
-
-
no enzyme activity detected with D-phenylalanine, L-5-hydroxytryptophan or L-histidine
-
?
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
?
-
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
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
O61717, O61718
-
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
O88533
biosynthesis of catecholamine neurotransmitters and serotonin
-
-
?
L-tryptophan
tryptamine + CO2
P93082
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
P17770
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
?
-
O61717
enzyme is involved in the production of melanin, a complex biochemical process in which several enzymes may play a role
-
-
-
additional information
?
-
O61718
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
?
-
O45216
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
?
-
O45216
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
?
-
O88533
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
-
-
-
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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
-
(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
pyridoxal 5'-phosphate
-
one pyridoxal 5'-phosphate cofactor per dimer structure
pyridoxal 5'-phosphate
-
-
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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INHIBITORS
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
O45216;
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
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
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
O45216;
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
-
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
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
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
O45216;
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