Bioactivation of Catha edulis alkaloids: enzymatic ketonization of norpseudoephedrine.
Bioactivation of Catha edulis alkaloids: enzymatic ketonization of norpseudoephedrine.
复制标题
郁金香生物碱的生物活化：去甲伪麻黄碱的酶促酮化。
DOI：
10.1016/0006-291x(82)91937-4
复制
发表时间：
1982
影响因子：
3.1
通讯作者：
Mueller,PW
中科院分区：
文献类型：
--
作者：
May,SW;Phillips,RS;Herman,HH;Mueller,PW
在已显示具有有效中枢神经系统刺激活性的苯基烷基胺中，有（+）-去甲伪麻黄碱及其酮类似物卡西酮，最近的研究表明卡西酮是这两种药物中更有效的药物。我们发现（+）-去甲伪麻黄碱被多巴胺-β-羟化酶氧化，生成卡西酮，其电子与O2的化学计量比为2：1：1，这是单加氧酶催化的反应。得到的kcat值为10 sec-1，Km为18.8 m M，表明该反应进行得足够快，具有生理学意义。（+）-去甲伪麻黄碱起效延迟和作用持续时间长与酶活化的要求一致，因此可能是多巴胺-β-羟化酶催化的酮化介导了该化合物和相关化合物的强效刺激作用。
Among the phenylalkylamines which have been shown to have potent central nervous system stimulatory activity are (+)-norpseudoephedrine and its ketone analog, cathinone, and recent work has suggested that cathinone is the more potent agent of the two. We have found that (+)-norpseudoephedrine is oxygenated by dopamine-β-hydroxylase, producing cathinone with the expected stoichiometry of electrons to O 2 to product of 2: 1: 1 diagnostic of a monooxygenase-catalyzed reaction. A k cat value of 10 sec− 1 and K m of 18.8 m M were obtained, indicating that this reaction proceeds readily enough to be of physiological significance. The delayed onset and long duration of action of (+)-norpseudoephedrine is consistent with a requirement for enzyme activation and thus it is possible that dopamine-β-hydroxylase-catalyzed ketonization mediates the potent stimulatory effect of this and related compounds.