Aromatic L-amino acid decarboxylase
Ribbon diagram of a DOPA decarboxylase dimer.
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|DOPA decarboxylase (aromatic L-amino acid decarboxylase)|
|Locus||Chr. 7 p11|
- Reactions 1
- As a rate-limiting step 2
- Genetics 3
- See also 4
- References 5
- External links 6
It catalyzes several different decarboxylation reactions:
- L-DOPA to dopamine - a neurotransmitter
- 5-HTP to serotonin (5-HT) - a neurotransmitter
- L-histidine to histamine - a neurotransmitter
- phenylalanine to phenethylamine - trace amine neurotransmitter
- L-tyrosine to tyramine - trace amine neurotransmitter
- tryptophan to tryptamine - trace amine neurotransmitter
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.
The gene encoding the enzyme is referred to as DDC and located on chromosome 7 in humans. 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 autism. No direct correlation between gene variation and autism was found.
- ; 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.
- Logan, Carolynn M.; Rice, M. Katherine (1987). Logan's Medical and Scientific Abbreviations. Philadelphia:
- "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.
- Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281.
- 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".
- 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".
- 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".
- Aromatic-L-Amino-Acid Decarboxylases at the US National Library of Medicine Medical Subject Headings (MeSH)