Aromatic L-amino acid decarboxylase

aromatic-L-amino-acid decarboxylase
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
Search PMC articles PubMed articles

DOPA decarboxylase (aromatic L-amino acid decarboxylase)
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.

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.

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.

   

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[2]

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Nicotine Activity on Dopaminergic Neurons 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]

See also

• Aromatic amino acids

References

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. ^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602. 
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

• MeSH Aromatic-L-Amino-Acid+Decarboxylases