Kostrzewa R M, Brus R
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, USA.
Amino Acids. 1998;14(1-3):175-9. doi: 10.1007/BF01345259.
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 like beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA) alpha-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.
在胺氧化酶活性位点发现的氨基酸6-羟基多巴胺（6-OHDOPA）以酮-烯醇形式存在。外源性给予的6-OHDOPA是一种兴奋性毒素，类似于β-N-草酰氨基-L-丙氨酸（BOAA）和β-N-甲基氨基-L-丙氨酸（BMAA），作用于非N-甲基-D-天冬氨酸（非NMDA）α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体。BMAA和BOAA是人类神经性豆状核变性的致病因素。外源性给予的大量6-OHDOPA会被氨基酸脱羧酶（AADC）生物转化为高效且对儿茶酚胺（CA）具有选择性的神经毒素6-羟基多巴胺（6-OHDA）。6-OHDOPA会破坏蓝斑去甲肾上腺素能神经元胞体，并导致含去甲肾上腺素（NE）的纤维对大脑产生相关的去神经支配。阿片肽和阿片类药物通过一种可被纳洛酮逆转的过程增强6-OHDOPA对去甲肾上腺素能神经的神经毒性作用。了解6-OHDOPA神经毒性作用的潜在机制有助于明确已知和新发现氨基酸的作用，并有助于研究它们潜在的神经毒性特性。
