Aromatic L-amino acid decarboxylase

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aromatic-L-amino-acid decarboxylase
DOPA decarboxylase dimer 1JS3.png
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
DOPA decarboxylase (aromatic L-amino acid decarboxylase)
Identifiers
Symbol DDC
Entrez 1644
HUGO 2719
OMIM 107930
RefSeq NM_000790
UniProt P20711
Other data
Locus Chr. 7 p11

Aromatic L-amino acid decarboxylase (EC 4.1.1.28, synonyms: DOPA decarboxylase, tryptophan decarboxylase, 5-hydroxytryptophan decarboxylase, AAAD,[2] AADC) is a lyase enzyme.

Reactions[edit]

It catalyzes several different decarboxylation reactions:

The enzyme uses pyridoxal phosphate, the active form of vitamin B6, as a cofactor.

As a rate-limiting step[edit]

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.

dopamine   serotonin

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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NicotineDopaminergic_WP1602 go to article go to article go to article Go to article go to article Go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article Go to article Go to article go to article Go to article Go to article Go to article go to article Go to article Go to article Go to article go to article go to article go to article go to article go to article go to article Go to article go to article Go to article Go to article go to article go to article Go to article go to article Go to article Go to article go to article
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Nicotine Activity on Dopaminergic Neurons edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". 

Genetics[edit]

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. No direct correlation between gene variation and autism was found.[5]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ Logan, Carolynn M.; Rice, M. Katherine (1987). Logan's Medical and Scientific Abbreviations. Philadelphia: J. B. Lippincott Company. p. 3. ISBN 0-397-54589-4. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 

External links[edit]