| 词条 | Aromatic L-amino acid decarboxylase |
| 释义 |
| Name = Aromatic L amino acid decarboxylase (DOPA 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 dimer.[1] }}{{infobox protein | Name = DOPA decarboxylase (aromatic L-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 L-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}}). ReactionsAADC catalyzes several different decarboxylation reactions:[2]
The enzyme uses pyridoxal phosphate, the active form of vitamin B6, as a cofactor. {{Phenylalanine biosynthesis|align=left}}{{clear left}}As a rate-limiting stepIn 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 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 amines. 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).[3] 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).[4] GeneticsThe gene encoding the enzyme is referred to as DDC and located on chromosome 7 in humans.[5] 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[6] and autism. No direct correlation between gene variation and autism was found.[7] See also
References1. ^{{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 }} 2. ^{{cite web|title=AADC|url=http://www.hmdb.ca/proteins/HMDBP00278|website=Human Metabolome database|accessdate=17 February 2015}} 3. ^{{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 }} 4. ^{{cite web|title=Patient registry|url=http://intd-online.org/}} 5. ^{{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 }} 6. ^{{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 }} 7. ^{{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 | pmc = 4826443 }} External links
1 : EC 4.1.1 |
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