Aromatic L-amino acid decarboxylase
| aromatic-L-amino-acid decarboxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||
| EC number | 4.1.1.28 | ||||||||
| CAS number | Template:CAS | ||||||||
| 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 | ||||||||
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| 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,[2] AADC) is a lyase enzyme.
Reactions
It catalyzes several different decarboxylation reactions:[3]
- 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
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.
In humans, AAAD is also the rate-limiting enzyme in the formation of trace amine neurotransmitters.
Genetics
The 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[7] and autism. No direct correlation between gene variation and autism was found.[8]
See also
References
- ↑ PDB: 1JS3; Lua error in package.lua at line 80: module 'strict' not found.
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External links
- Aromatic-L-Amino-Acid Decarboxylases at the US National Library of Medicine Medical Subject Headings (MeSH)
