Human monoamine oxidase enzyme inhibition by coffee and β-carbolines norharman and harman isolated from coffee
Human monoamine oxidase enzyme inhibition by coffee and β-carbolines norharman and harman isolated from coffee
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DOI：
10.1016/j.lfs.2005.05.074
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发表时间：
2006-01-18
期刊：
影响因子：
6.1
通讯作者：
Chaparro, C
中科院分区：
文献类型：
--
作者：
Herraiz, T;Chaparro, C
单胺氧化酶（Monoamine oxidase，MAO）是一种线粒体外膜黄素酶，参与神经递质和异生物胺（包括神经毒性胺）的脑和外周氧化催化，并且是抗抑郁和神经保护药物的众所周知的靶点。最近的流行病学研究一致表明，喝咖啡的人患帕金森病（PD）的发病率明显较低，这表明咖啡可能以某种方式起着所谓的神经保护剂的作用。在本文中，“即饮型”咖啡冲泡物对催化犬尿胺氧化脱氨基的重组人MAO A和B同工酶表现出抑制特性，表明咖啡含有充当MAO抑制剂的化合物。单胺氧化酶A和单胺氧化酶B对单胺氧化酶的抑制是可逆的和竞争性的。随后，从单胺氧化酶抑制咖啡中鉴定并分离了吡啶并吲哚（β-咔啉）生物碱norharman和harman，它们是对单胺氧化酶A（harman和norharman）和单胺氧化酶B（norharman）同工酶的良好抑制剂。从即饮咖啡中分离的β-咔啉是竞争性和可逆的抑制剂，并且高达210 μ g/L，证实了咖啡是除吸烟之外这些生物碱的最重要的外源性来源。咖啡对单胺氧化酶的抑制作用以及具有神经活性的单胺氧化酶抑制剂（如β-咔啉等）的存在，可能在神经活性作用中发挥作用，包括与咖啡消费相关的据称的神经保护作用。(c)2005年爱思唯尔公司All rights reserved.
Monoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic amines, including neurotoxic amines, and a well-known target for antidepressant and neuroprotective drugs. Recent epidemiological studies have consistently shown that coffee drinkers have an apparently lower incidence of Parkinson's disease (PD), suggesting that coffee might somehow act as a purported neuroprotectant. In this paper, "ready to drink" coffee brews exhibited inhibitory properties on recombinant human MAO A and B isozymes catalyzing the oxidative deamination of kynuramine, suggesting that coffee contains compounds acting as MAO inhibitors. MAO inhibition was reversible and competitive for MAO A and MAO B. Subsequently, the pyrido-indole (beta-carboline) alkaloids, norharman and harman, were identified and isolated from MAO-inhibiting coffee, and were good inhibitors on MAO A (harman and norharman) and MAO B (norharman) isozymes. beta-carbolines isolated from ready-to-drink coffee were competitive and reversible inhibitors and appeared up to 210 mu g/L, confirming that coffee is the most important exogenous source of these alkaloids in addition to cigarette smoking. Inhibition of MAO enzymes by coffee and the presence of MAO inhibitors that are also neuroactive, such as beta-carbolines and eventually others, might play a role in the neuroactive actions including a purported neuroprotection associated with coffee consumption. (c) 2005 Elsevier Inc. All rights reserved.