Summary
The amino acid, 6-hydroxydopa (6-OHDOPA), found at the active site of amine oxidases, exists as a keto-enol. Exogenously administered 6-OHDOPA is an excitotoxin likeβ-N-oxalylamino-L-alanine (BOAA) andβ-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA)α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. BMAA and BOAA are causal factors of neurolathyrism in humans. Much exogenously administered 6-OHDOPA is biotransformed by aminoacid decarboxylase (AADC) to the highly potent and catecholamine (CA) selective neurotoxin, 6-hydroxydopamine (6-OHDA). 6-OHDOPA destroys locus coeruleus noradrenergic perikarya and produces associated denervation of brain by norepinephrine-(NE) containing fibers. Opiopeptides and opioids enhance neurotoxic effects of 6-OHDOPA on noradrenergic nerves, by a naloxone-reversible process. An understanding of mechanisms underlying neurotoxic effects of 6-OHDOPA can be helpful in defining actions of known and newfound amino acids and for investigating their potential neurotoxic properties.
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Abbreviations
- AADC:
-
aminoacid decarboxylase
- AMPA:
-
α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
- BOAA:
-
β-N-oxalylamino-Lalanine
- CA:
-
catecholamine
- L-DOPA:
-
L-dihydroxyphenylalanine
- DA:
-
dopamine
- EAA:
-
excitatory amino acid
- 6-OHDOPA:
-
6-hydroxydopa
- 6-OHDA:
-
6-hydroxydopamine
- NE:
-
norepinephrine
- BMAA:
-
β-N-methylamino-L-alanine
- NMDA:
-
N-methyl-D-aspartate
- S.E.M.:
-
standard error of the mean
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Kostrzewa, R.M., Brus, R. Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor. Amino Acids 14, 175–179 (1998). https://doi.org/10.1007/BF01345259
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DOI: https://doi.org/10.1007/BF01345259