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Literature summary for 4.1.1.28 extracted from
- Mammalian dopa decarboxylase structure, catalytic activity and inhibition (2014), Arch. Biochem. Biophys., 546, 1-7 .
Application
| Application | Comment | Organism |
|---|---|---|
| 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)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression in Escherichia coli | Homo sapiens |
| recombinant expression in Escherichia coli | Sus scrofa |
| recombinant expression in Escherichia coli | Rattus norvegicus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| Y332F | the mutant variant switches its reaction specificity from amine generation to aldehyde generation performing an oxidative deamination of L-Dopa | Sus scrofa |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| Amb2470350 | a reversible competitive inhibitor | Homo sapiens |  |
| Amb2470350 | a reversible competitive inhibitor | Rattus norvegicus | |
| Amb2470350 | a reversible competitive inhibitor | Sus scrofa | |
| Benserazide | - |
Homo sapiens | |
| carbidopa | Thr82 is implicated in 4'-hydroxyl catechol ring binding | Homo sapiens | |
| 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 | |
| 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 | |
| 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 | |
| serotonin | and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition | Homo sapiens | |
| serotonin | and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition | Rattus norvegicus | |
| serotonin | and/or its aldehyde, behaves as a mechanism-based inhibitor, product inhibition | Sus scrofa | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetics | Homo sapiens | |
| additional information | - |
additional information | Michaelis-Menten kinetics | Sus scrofa | |
| additional information | - |
additional information | Michaelis-Menten kinetics | Rattus norvegicus | |
| 0.028 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Homo sapiens | |
| 0.07 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Sus scrofa | |
| 0.086 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5-hydroxy-L-tryptophan | Homo sapiens | - |
5-hydroxytryptamine + CO2 | - |
? | |
| 5-hydroxy-L-tryptophan | Sus scrofa | - |
5-hydroxytryptamine + CO2 | - |
? | |
| 5-hydroxy-L-tryptophan | Rattus norvegicus | - |
5-hydroxytryptamine + CO2 | - |
? | |
| L-Dopa | Homo sapiens | - |
dopamine + CO2 | - |
? | |
| L-Dopa | Sus scrofa | - |
dopamine + CO2 | - |
? | |
| L-Dopa | Rattus norvegicus | - |
dopamine + CO2 | - |
? | |
| 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
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P20711 | - |
- |
| Rattus norvegicus | P14173 | - |
- |
| Sus scrofa | P80041 | - |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| L-dopa = dopamine + CO2 | decarboxylation reaction mechanism, overview | Homo sapiens | |
| L-dopa = dopamine + CO2 | decarboxylation reaction mechanism, overview | Sus scrofa | |
| 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 |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | dopamine-producing cells in the substantia nigra | Homo sapiens | - |
| brain | dopamine-producing cells in the substantia nigra | Sus scrofa | - |
| brain | dopamine-producing cells in the substantia nigra | Rattus norvegicus | - |
| kidney | - |
Homo sapiens | - |
| kidney | - |
Sus scrofa | - |
| kidney | - |
Rattus norvegicus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5-hydroxy-L-tryptophan | - |
Homo sapiens | 5-hydroxytryptamine + CO2 | - |
? | |
| 5-hydroxy-L-tryptophan | - |
Sus scrofa | 5-hydroxytryptamine + CO2 | - |
? | |
| 5-hydroxy-L-tryptophan | - |
Rattus norvegicus | 5-hydroxytryptamine + CO2 | - |
? | |
| L-Dopa | - |
Homo sapiens | dopamine + CO2 | - |
? | |
| L-Dopa | - |
Sus scrofa | dopamine + CO2 | - |
? | |
| L-Dopa | - |
Rattus norvegicus | dopamine + CO2 | - |
? | |
| L-Dopa | substrate ionization is related to the catalytic event | Homo sapiens | dopamine + CO2 | - |
? | |
| 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
| Subunits | Comment | Organism |
|---|---|---|
| dimer | - |
Homo sapiens |
| dimer | - |
Sus scrofa |
| dimer | - |
Rattus norvegicus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| AADC | - |
Homo sapiens |
| AADC | - |
Sus scrofa |
| AADC | - |
Rattus norvegicus |
| DDC | - |
Homo sapiens |
| DDC | - |
Sus scrofa |
| DDC | - |
Rattus norvegicus |
| DOPA decarboxylase | - |
Homo sapiens |
| DOPA decarboxylase | - |
Sus scrofa |
| DOPA decarboxylase | - |
Rattus norvegicus |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 5.1 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Homo sapiens | |
| 5.8 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Sus scrofa | |
| 6.3 | - |
L-Dopa | decarboxylation reaction, pH and temperature not specified in the publication | Rattus norvegicus | |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| pyridoxal 5'-phosphate | dependent on | Homo sapiens | |
| pyridoxal 5'-phosphate | dependent on | Sus scrofa | |
| pyridoxal 5'-phosphate | dependent on | Rattus norvegicus | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0005 | - |
Amb2470350 | pH and temperature not specified in the publication | Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| 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 |
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