Aromatic L-amino acid decarboxylase (EC 4.1.1.28, synonyms: DOPA decarboxylase, tryptophan decarboxylase, 5-hydroxytryptophan decarboxylase, AAAD, AADC) is a lyase enzyme.
Reactions
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
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. Single nucleotide polymorphisms and other gene variations have been investigated in relation to neuropsychiatric disorders, e.g., a one-base pair deletion at â€"601 and a four-base pair deletion at 722â€"725 in exon 1 in relation to bipolar disorder and autism. No direct correlation between gene variation and autism was found.
See also
- Aromatic amino acids
- Histidine decarboxylase
References
External links
- Aromatic-L-Amino-Acid Decarboxylases at the US National Library of Medicine Medical Subject Headings (MeSH)