View source for Aromatic L-amino acid decarboxylase

{{DISPLAYTITLE:Aromatic <small>L</small>-amino acid decarboxylase}}
{{enzyme
| Name = aromatic-<small>L</small>-amino-acid decarboxylase
| EC_number = 4.1.1.28
| CAS_number = 9042-64-2 
| IUBMB_EC_number = 4/1/1/28
| GO_code = 0004058
| image = DOPA decarboxylase dimer 1JS3.png
| width = 
| caption = Ribbon diagram of a DOPA decarboxylase [[protein dimer|dimer]].<ref name="pmid11685243">{{PDB|1JS3}}; {{cite journal | vauthors = Burkhard P, Dominici P, Borri-Voltattorni C, Jansonius JN, Malashkevich VN | title = Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase | journal = Nature Structural Biology | volume = 8 | issue = 11 | pages = 963–7 | date = Nov 2001 | pmid = 11685243 | doi = 10.1038/nsb1101-963 }}</ref>
}}
{{infobox protein
| Name = DOPA decarboxylase (aromatic <small>L</small>-amino acid decarboxylase)
| caption = 
| image = 
| width = 250
| HGNCid = 2719
| Symbol = DDC
| AltSymbols =
| EntrezGene = 1644
| OMIM = 107930
| RefSeq = NM_000790
| UniProt = P20711
| PDB =
| ECnumber = 4.1.1.28
| Chromosome = 7
| Arm = p
| Band = 11
| LocusSupplementaryData =
}}
'''Aromatic <small>L</small>-amino acid decarboxylase''' ('''AADC''' or '''AAAD'''), also known as '''DOPA decarboxylase''' ('''DDC'''), '''tryptophan decarboxylase''', and '''5-hydroxytryptophan decarboxylase''', is a [[lyase]] [[enzyme]] ({{EC number|4.1.1.28}}).

==Reactions==
AADC catalyzes several different [[decarboxylation]] reactions:<ref>{{cite web|title=AADC|url=http://www.hmdb.ca/proteins/HMDBP00278|website=Human Metabolome database|accessdate=17 February 2015}}</ref>
* [[L-DOPA]] to [[dopamine]] - a [[neurotransmitter]]
* [[L-phenylalanine]] to [[phenethylamine]] - a [[trace amine]] [[neuromodulator]]
* [[L-tyrosine]] to [[tyramine]] - a trace amine neuromodulator
* [[L-histidine]] to [[histamine]] - a neurotransmitter
* [[L-tryptophan]] to [[tryptamine]] - a trace amine neuromodulator
* [[5-HTP]] to [[serotonin]] (5-hydroxytryptamine) - a neurotransmitter

The enzyme uses [[pyridoxal phosphate]], the active form of [[vitamin B6|vitamin B<sub>6</sub>]], as a [[cofactor (biochemistry)|cofactor]].
{{Phenylalanine biosynthesis|align=left}}
[[File:Serotonin biosynthesis.svg|thumb|right|360px|Human serotonin biosynthesis pathway]]
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==As a rate-limiting step==
In normal [[dopamine]] and [[serotonin]] (5-HT) neurotransmitter synthesis, AADC is not the [[rate-limiting step]] in either reaction. However, AADC 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 [[Clinical depression|depression]] or [[dysthymia]]).  AADC 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]].

In humans, AADC is also the [[rate-limiting enzyme]] in the formation of [[trace amine]]s.
Deficiency of AADC is associated with various symptoms as severe developmental delay, [[oculogyric crises]] and autonomic dysfunction. The molecular and clinical spectrum of AAAC deficiency is heterogeneous. The first case of AADC deficiency was described in twin brothers 1990. Patients can be treated with [[dopamine agonists]], [[MAO inhibitors]], and [[pyridoxine]] ([[vitamin B6|vitamin B<sub>6</sub>]]).<ref>{{cite journal | vauthors = Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC | title = Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis | journal = Neurology | volume = 62 | issue = 7 | pages = 1058–65 | date = Apr 2004 | pmid = 15079002 | doi = 10.1212/WNL.62.7.1058 }}</ref> Clinical phenotype and response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).<ref>{{cite web|title=Patient registry|url=http://intd-online.org/}}</ref>

== Genetics ==
The [[gene]] encoding the enzyme is referred to as ''DDC'' and located on [[chromosome 7]] in humans.<ref>{{cite journal | vauthors = Scherer LJ, McPherson JD, Wasmuth JJ, Marsh JL | title = Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs | journal = Genomics | volume = 13 | issue = 2 | pages = 469–71 | date = Jun 1992 | pmid = 1612608 | doi = 10.1016/0888-7543(92)90275-W }}</ref> [[Single nucleotide polymorphism]]s and other gene variations have been investigated in relation to [[neuropsychiatric disorder]]s, e.g., a one-base pair deletion at &ndash;601 and a four-base pair deletion at 722&ndash;725 in [[exon]] 1 in relation to [[bipolar disorder]]<ref>{{cite journal | vauthors = Børglum AD, Bruun TG, Kjeldsen TE, Ewald H, Mors O, Kirov G, Russ C, Freeman B, Collier DA, Kruse TA | title = Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder | journal = Molecular Psychiatry | volume = 4 | issue = 6 | pages = 545–51 | date = Nov 1999 | pmid = 10578236 | doi = 10.1038/sj.mp.4000559 }}</ref> and [[autism]]. No direct correlation between gene variation and autism was found.<ref>{{cite journal | vauthors = Lauritsen MB, Børglum AD, Betancur C, Philippe A, Kruse TA, Leboyer M, Ewald H | title = Investigation of two variants in the DOPA decarboxylase gene in patients with autism | journal = American Journal of Medical Genetics | volume = 114 | issue = 4 | pages = 466–70 | date = May 2002 | pmid = 11992572 | doi = 10.1002/ajmg.10379 }}</ref>

== See also ==
* [[Aromatic L-amino acid decarboxylase inhibitor]], a class of anti-Parkinson drugs
* [[Aromatic amino acids]]
* [[Histidine decarboxylase]]
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== References ==
{{Reflist|33em}}

== External links ==
* {{MeshName|Aromatic-L-Amino-Acid+Decarboxylases}}

{{Neurotransmitter metabolism enzymes}}
{{Carbon-carbon lyases}}
{{Enzymes}}
{{Monoamine metabolism modulators}}
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[[Category:EC 4.1.1]]