Aromatic L-amino acid decarboxylase ( EC 18.104.22.168, synonyms: DOPA decarboxylase, , tryptophan decarboxylase 5-hydroxytryptophan decarboxylase, AAAD, [2 ] AADC) is a lyase enzyme.
Reactions [ edit ]
It catalyzes several different
decarboxylation reactions: [3 ]
The enzyme uses
pyridoxal phosphate, the active form of vitamin B6, as a cofactor.
Human biosynthesis pathway for trace amines and catecholamines
[4 ] [5 ]
Human serotonin biosynthesis pathway
As a rate-limiting step [ edit ]
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.
In humans, AAAD is also the
rate-limiting enzyme in the formation of trace amine neurotransmitters.
Genetics [ edit ]
gene encoding the enzyme is referred to as DDC and located on chromosome 7 in humans. [6 ] 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 and [7 ] autism. No direct correlation between gene variation and autism was found. [8 ]
See also [ edit ]
References [ edit ]
^ ; 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.
^ 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.
^ "AADC". Human Metabolome database . Retrieved . 17 February 2015
^ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi: 10.1016/j.pharmthera.2009.11.005. PMID 19948186.
^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi: 10.1016/j.tips.2005.03.007. PMID 15860375.
^ 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.
External links [ edit ]