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Literature summary extracted from

  • Bertoldi, M.
    Mammalian dopa decarboxylase structure, catalytic activity and inhibition (2014), Arch. Biochem. Biophys., 546, 1-7 .
    View publication on PubMed

Application

EC Number Application Comment Organism
4.1.1.28 drug development the enzyme is a target for drug development in the therapy of either Parkinson's disease or aromatic amino acid decarboxylase deficiency Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
4.1.1.28 recombinant expression in Escherichia coli Homo sapiens
4.1.1.28 recombinant expression in Escherichia coli Sus scrofa
4.1.1.28 recombinant expression in Escherichia coli Rattus norvegicus

Protein Variants

EC Number Protein Variants Comment Organism
4.1.1.28 Y332F the mutant variant switches its reaction specificity from amine generation to aldehyde generation performing an oxidative deamination of L-Dopa Sus scrofa

Inhibitors

EC Number Inhibitors Comment Organism Structure
4.1.1.28 Amb2470350 a reversible competitive inhibitor Homo sapiens
4.1.1.28 Amb2470350 a reversible competitive inhibitor Rattus norvegicus
4.1.1.28 Amb2470350 a reversible competitive inhibitor Sus scrofa
4.1.1.28 Benserazide
-
 Homo sapiens
4.1.1.28 carbidopa Thr82 is implicated in 4'-hydroxyl catechol ring binding Homo sapiens
4.1.1.28 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 Homo sapiens
4.1.1.28 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 Rattus norvegicus
4.1.1.28 additional information 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 Sus scrofa
4.1.1.28 serotonin and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition Homo sapiens
4.1.1.28 serotonin and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition Rattus norvegicus
4.1.1.28 serotonin and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition Sus scrofa

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
4.1.1.28 additional information
-
 additional information Michaelis-Menten kinetics Homo sapiens
4.1.1.28 additional information
-
 additional information Michaelis-Menten kinetics Sus scrofa
4.1.1.28 additional information
-
 additional information Michaelis-Menten kinetics Rattus norvegicus
4.1.1.28 0.028
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Homo sapiens
4.1.1.28 0.07
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Sus scrofa
4.1.1.28 0.086
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.1.1.28 5-hydroxy-L-tryptophan Homo sapiens
-
 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 5-hydroxy-L-tryptophan Sus scrofa
-
 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 5-hydroxy-L-tryptophan Rattus norvegicus
-
 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 L-Dopa Homo sapiens
-
 dopamine + CO2
-
 ?
4.1.1.28 L-Dopa Sus scrofa
-
 dopamine + CO2
-
 ?
4.1.1.28 L-Dopa Rattus norvegicus
-
 dopamine + CO2
-
 ?
4.1.1.28 additional information Sus scrofa 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 ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
4.1.1.28 Homo sapiens P20711
-
-
4.1.1.28 Rattus norvegicus P14173
-
-
4.1.1.28 Sus scrofa P80041
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
4.1.1.28 L-dopa = dopamine + CO2 decarboxylation reaction mechanism, overview Homo sapiens
a
4.1.1.28 L-dopa = dopamine + CO2 decarboxylation reaction mechanism, overview Sus scrofa
a
4.1.1.28 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 Rattus norvegicus
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
4.1.1.28 brain dopamine-producing cells in the substantia nigra Homo sapiens
-
4.1.1.28 brain dopamine-producing cells in the substantia nigra Sus scrofa
-
4.1.1.28 brain dopamine-producing cells in the substantia nigra Rattus norvegicus
-
4.1.1.28 kidney
-
 Homo sapiens
-
4.1.1.28 kidney
-
 Sus scrofa
-
4.1.1.28 kidney
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.1.1.28 5-hydroxy-L-tryptophan
-
 Homo sapiens 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 5-hydroxy-L-tryptophan
-
 Sus scrofa 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 5-hydroxy-L-tryptophan
-
 Rattus norvegicus 5-hydroxytryptamine + CO2
-
 ?
4.1.1.28 L-Dopa
-
 Homo sapiens dopamine + CO2
-
 ?
4.1.1.28 L-Dopa
-
 Sus scrofa dopamine + CO2
-
 ?
4.1.1.28 L-Dopa
-
 Rattus norvegicus dopamine + CO2
-
 ?
4.1.1.28 L-Dopa substrate ionization is related to the catalytic event Homo sapiens dopamine + CO2
-
 ?
4.1.1.28 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 Sus scrofa ?
-
 ?

Subunits

EC Number Subunits Comment Organism
4.1.1.28 dimer
-
 Homo sapiens
4.1.1.28 dimer
-
 Sus scrofa
4.1.1.28 dimer
-
 Rattus norvegicus

Synonyms

EC Number Synonyms Comment Organism
4.1.1.28 AADC
-
 Homo sapiens
4.1.1.28 AADC
-
 Sus scrofa
4.1.1.28 AADC
-
 Rattus norvegicus
4.1.1.28 DDC
-
 Homo sapiens
4.1.1.28 DDC
-
 Sus scrofa
4.1.1.28 DDC
-
 Rattus norvegicus
4.1.1.28 DOPA decarboxylase
-
 Homo sapiens
4.1.1.28 DOPA decarboxylase
-
 Sus scrofa
4.1.1.28 DOPA decarboxylase
-
 Rattus norvegicus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
4.1.1.28 5.1
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Homo sapiens
4.1.1.28 5.8
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Sus scrofa
4.1.1.28 6.3
-
 L-Dopa decarboxylation reaction, pH and temperature not specified in the publication Rattus norvegicus

Cofactor

EC Number Cofactor Comment Organism Structure
4.1.1.28 pyridoxal 5'-phosphate dependent on Homo sapiens
4.1.1.28 pyridoxal 5'-phosphate dependent on Sus scrofa
4.1.1.28 pyridoxal 5'-phosphate dependent on Rattus norvegicus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
4.1.1.28 0.0005
-
 Amb2470350 pH and temperature not specified in the publication Homo sapiens

General Information

EC Number General Information Comment Organism
4.1.1.28 physiological function mammalian Dopa decarboxylase catalyzes the conversion of L-Dopa and L-5 hydroxytryptophan to dopamine and serotonin, respectively. Both of them are biologically active neurotransmitters whose levels has to be finely tuned. An altered concentration of dopamine is the cause of neurodegenerative diseases, such as Parkinson's disease. Enzyme DDC is not considered to be rate-limiting in physiological catecholamines or indoleamines synthesis, but it becomes rate-limiting in several pathological states related to aberrant dopamine production, such as Parkinson's disease (PD) or the bipolar syndrome. PD is a chronic progressive neurological disorder characterized by tremor, bradykinesia, rigidity and postural instability. These symptons are caused by the low levels of dopamine resulting from the degeneration of dopamine-producing cells in the substantia nigra of the brain Homo sapiens
4.1.1.28 physiological function mammalian Dopa decarboxylase catalyzes the conversion of L-Dopa and L-5 hydroxytryptophan to dopamine and serotonin, respectively. Both of them are biologically active neurotransmitters whose levels has to be finely tuned. Enzyme DDC is not considered to be rate-limiting in physiological catecholamines or indoleamines synthesis Rattus norvegicus
4.1.1.28 physiological function mammalian Dopa decarboxylase catalyzes the conversion of L-Dopa and L-5 hydroxytryptophan to dopamine and serotonin, respectively. Both of them are biologically active neurotransmitters whose levels has to be finely tuned. Enzyme DDC is not considered to be rate-limiting in physiological catecholamines or indoleamines synthesis. The aromatic compounds produced by oxidative deamination through the enzyme possess similar biological activities as the aromatic amines and thus are strong biologically active signals Sus scrofa