Aromatic L-amino acid decarboxylase
| aromatic-L-amino-acid decarboxylase | |||||||
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| Ribbon diagram of a domestic pig DOPA decarboxylase dimer.[1] | |||||||
| Identifiers | |||||||
| EC number | 4.1.1.28 | ||||||
| CAS number | 9042-64-2 | ||||||
| Databases | |||||||
| IntEnz | IntEnz view | ||||||
| BRENDA | BRENDA entry | ||||||
| ExPASy | NiceZyme view | ||||||
| KEGG | KEGG entry | ||||||
| MetaCyc | metabolic pathway | ||||||
| PRIAM | profile | ||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||
| Gene Ontology | AmiGO / EGO | ||||||
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| DOPA decarboxylase (aromatic L-amino acid decarboxylase) | |
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| Identifiers | |
| Symbol | DDC |
| Entrez | 1644 |
| HUGO | 2719 |
| OMIM | 107930 |
| RefSeq | NM_000790 |
| UniProt | P20711 |
| Other data | |
| EC number | 4.1.1.28 |
| Locus | Chr. 7 p11 |
Aromatic L-amino acid decarboxylase (EC 4.1.1.28, synonyms: DOPA decarboxylase, tryptophan decarboxylase, 5-hydroxytryptophan decarboxylase, AAAD) is a lyase enzyme.
Contents |
[edit] Reactions
It catalyzes several different decarboxylation reactions:
- L-DOPA to dopamine - a neurotransmitter
- 5-HTP to serotonin (5-HT) - also a neurotransmitter
- tryptophan to tryptamine - a precursor to many alkaloids found in plants and animals
The enzyme uses pyridoxal phosphate, the active form of vitamin B6, as a cofactor.
[edit] As a rate-limiting step
In normal dopamine and serotonin (5-HT) neurotransmitter synthesis, AAAD is not the rate-limiting step in either reaction. However, AAAD becomes the rate-limiting step of dopamine synthesis in patients treated with L-DOPA (such as in Parkinson's Disease), and the rate-limiting step of serotonin synthesis in people treated with 5-HTP (such as in mild depression or dysthymia). AAAD is inhibited by Carbidopa outside of the blood brain barrier to inhibit the premature conversion of L-DOPA to Dopamine in the treatment of Parkinson's.
AAAD is the rate-limiting enzyme in the formation of biogenic trace amines.
[edit] Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [2]
[edit] Genetics
The gene encoding the enzyme is referred to as DDC and located on chromosome 7 in humans.[3] Single nucleotide polymorphisms and other gene variations have been investigated in relation to neuropsychiatric disorders, e.g., a one-base pair deletion at –601 and a four-base pair deletion at 722–725 in exon 1 in relation to bipolar disorder[4] and autism.[5]
[edit] See also
[edit] References
- ^ PDB 1JS3; Burkhard P, Dominici P, Borri-Voltattorni C, Jansonius JN, Malashkevich VN (November 2001). "Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase". Nat. Struct. Biol. 8 (11): 963–7. doi:10.1038/nsb1101-963. PMID 11685243.
- ^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602.
- ^ Lisa J. Scherer, John D. McPherson, John J. Wasmuth and J. Lawrence Marsh (June 1992). "Human dopa decarboxylase: Localization to human chromosome 7p11 and characterization of hepatic cDNAs". Genomics 13 (2): 469–471. doi:10.1016/0888-7543(92)90275-W. PMID 1612608.
- ^ A. D. Borglum, T. G. Bruun, T. E. Kjeldsen, H. Ewald, O. Mors, G. Kirov, C. Russ, B. Freeman, D. A. Collier & T. A. Kruse (November 1999). "Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder". Molecular Psychiatry 4 (6): 545–541. doi:10.1038/sj.mp.4000559. PMID 10578236.
- ^ Marlene B. Lauritsen, Anders D. Borglum, Catalina Betancur, Anne Philippe, Torben A. Kruse, Marion Leboyer & Henrik Ewald (May 2002). "Investigation of two variants in the DOPA decarboxylase gene in patients with autism". American Journal of Medical Genetics 114 (4): 466–460. doi:10.1002/ajmg.10379. PMID 11992572.
[edit] External links
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