1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对大鼠肝脏单胺氧化酶-B的氧化及酶激活不可逆抑制作用
Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
作者信息
Tipton K F, McCrodden J M, Youdim M B
出版信息
Biochem J. 1986 Dec 1;240(2):379-83. doi: 10.1042/bj2400379.
Abstract
The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces symptoms resembling Parkinson's disease in humans, acts both as a substrate and an enzyme-activated irreversible inhibitor of the B-form of monoamine oxidase from rat liver. Analysis of the inhibitory process showed the compound to be considerably more efficient as a substrate than as an irreversible inhibitor, with about 17000 mol of product being formed per mol of enzyme inactivated. The half-time of the inhibitory process was about 22 min. With the A-form of the enzyme, the compound had a lower Km value and a considerably lower maximum velocity than the corresponding values obtained with the B-form. Under the conditions used in the present work the inhibition of the A-form of the enzyme was largely reversible.
摘要
化合物1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）可在人类身上引发类似帕金森病的症状，它既是大鼠肝脏中B型单胺氧化酶的底物，也是一种酶激活的不可逆抑制剂。对抑制过程的分析表明，该化合物作为底物的效率远高于作为不可逆抑制剂的效率，每摩尔失活的酶大约会形成17000摩尔的产物。抑制过程的半衰期约为22分钟。对于A型酶，该化合物的米氏常数（Km值）较低，最大反应速度也明显低于B型酶的相应值。在本研究使用的条件下，A型酶的抑制作用在很大程度上是可逆的。
相似文献
1
Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对大鼠肝脏单胺氧化酶-B的氧化及酶激活不可逆抑制作用
Biochem J. 1986 Dec 1;240(2):379-83. doi: 10.1042/bj2400379.
2
The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-(4-[(3-chlorophenyl)methoxy]phenyl)-5-[(methylamino) methyl]-2-oxazolidinone methanesulphonate (compound MD 780236) and the enzyme-catalysed oxidation of this compound as competing reactions.3-(4-[(3-氯苯基)甲氧基]苯基)-5-[(甲氨基)甲基]-2-恶唑烷酮甲磺酸盐（化合物MD 780236）对B型单胺氧化酶的酶激活不可逆抑制作用以及该化合物的酶催化氧化作为竞争反应。
Biochem J. 1983 Jan 1;209(1):235-42. doi: 10.1042/bj2090235.
3
Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP.单胺氧化酶A和B对神经毒性胺1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的氧化作用以及MPTP对这些酶的自杀性失活作用。
Biochem Biophys Res Commun. 1984 Dec 14;125(2):831-5. doi: 10.1016/0006-291x(84)90614-4.
4
The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline.炔丙型抑制剂氯吉兰、l-司来吉兰和帕吉林对大鼠肝脏A型和B型单胺氧化酶的抑制性质。
Biochem Pharmacol. 1982 Nov 15;31(22):3555-61. doi: 10.1016/0006-2952(82)90575-5.
5
Prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic toxicity in mice by MDL 72145, a selective inhibitor of MAO-B.单胺氧化酶B选择性抑制剂MDL 72145预防1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的小鼠多巴胺能毒性。
Life Sci. 1986 Apr 21;38(16):1459-62. doi: 10.1016/0024-3205(86)90558-8.
6
Reversible inhibition and mechanism-based irreversible inactivation of monoamine oxidases by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对单胺氧化酶的可逆抑制及基于机制的不可逆失活
Biochem Biophys Res Commun. 1985 Mar 15;127(2):707-12. doi: 10.1016/s0006-291x(85)80219-9.
7
Substrate specificity of the different forms of monoamine oxidase in rat liver mitochondria.大鼠肝脏线粒体中不同形式单胺氧化酶的底物特异性。
Biochem Pharmacol. 1976 May 15;25(10):1133-8. doi: 10.1016/0006-2952(76)90359-2.
8
Studies on the oxidation of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase B.单胺氧化酶B对多巴胺能神经毒素1-甲基-4-苯基-1,2,5,6-四氢吡啶氧化作用的研究。
J Neurochem. 1985 Oct;45(4):1049-54. doi: 10.1111/j.1471-4159.1985.tb05522.x.
9
Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases.神经毒性胺1-甲基-4-苯基-1,2,3,6-四氢吡啶与单胺氧化酶的相互作用。
Biochem J. 1986 May 1;235(3):785-9. doi: 10.1042/bj2350785.
10
Monoamine oxidase B(MAO-B) is the major catalyst for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) oxidation in human brain and other tissues.单胺氧化酶B（MAO-B）是人类大脑和其他组织中1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）氧化的主要催化剂。
Neurosci Lett. 1986 Feb 28;64(2):216-20. doi: 10.1016/0304-3940(86)90103-5.
引用本文的文献
1
90 years of monoamine oxidase: some progress and some confusion.90 年的单胺氧化酶：一些进展和一些困惑。
J Neural Transm (Vienna). 2018 Nov;125(11):1519-1551. doi: 10.1007/s00702-018-1881-5. Epub 2018 Apr 10.
2
Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs.酶抑制作用的评估：以单胺氧化酶和胆碱酯酶抑制药物开发为例的综述
Molecules. 2017 Jul 15;22(7):1192. doi: 10.3390/molecules22071192.
3
Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines.四氢吡啶和二氢吡啶对单胺氧化酶A和B的基于机制的失活作用
Biochem J. 1990 May 15;268(1):219-24. doi: 10.1042/bj2680219.
4
Interactions of the neurotoxin MPTP and its demethylated derivative (PTP) with monoamine oxidase-B.神经毒素MPTP及其去甲基化衍生物（PTP）与单胺氧化酶-B的相互作用。
Neurochem Res. 1992 Aug;17(8):791-6. doi: 10.1007/BF00969014.
本文引用的文献
1
RADIOISOTOPIC ASSAY FOR MONOAMINE OXIDASE DETERMINATIONS IN HUMAN PLASMA.用于测定人血浆中单胺氧化酶的放射性同位素分析
Biochem Pharmacol. 1964 Jul;13:995-1006. doi: 10.1016/0006-2952(64)90096-6.
2
Purification of amine oxidase from beef plasma.从牛血浆中纯化胺氧化酶。
J Biol Chem. 1954 Jun;208(2):645-61.
3
Kinetics of suicide substrates.自杀底物的动力学
Biochem J. 1980 Mar 1;185(3):771-3. doi: 10.1042/bj1850771.
4
Concentration dependence of the oxidation of tyramine by the two forms of rat liver mitochondrial monoamine oxidase.两种形式的大鼠肝脏线粒体单胺氧化酶对酪胺氧化的浓度依赖性
Biochem Pharmacol. 1981 Dec 15;30(24):3329-32. doi: 10.1016/0006-2952(81)90607-9.
5
Kinetics of suicide substrates. Steady-state treatments and computer-aided exact solutions.自杀底物的动力学。稳态处理与计算机辅助精确解
Biochim Biophys Acta. 1981 Dec 15;662(2):226-35. doi: 10.1016/0005-2744(81)90034-6.
6
The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-(4-[(3-chlorophenyl)methoxy]phenyl)-5-[(methylamino) methyl]-2-oxazolidinone methanesulphonate (compound MD 780236) and the enzyme-catalysed oxidation of this compound as competing reactions.3-(4-[(3-氯苯基)甲氧基]苯基)-5-[(甲氨基)甲基]-2-恶唑烷酮甲磺酸盐（化合物MD 780236）对B型单胺氧化酶的酶激活不可逆抑制作用以及该化合物的酶催化氧化作为竞争反应。
Biochem J. 1983 Jan 1;209(1):235-42. doi: 10.1042/bj2090235.
7
Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.人类因哌替啶类似物合成产物导致的慢性帕金森症。
Science. 1983 Feb 25;219(4587):979-80. doi: 10.1126/science.6823561.
8
The monoamine oxidase inhibiting properties of CGP 11305 A.CGP 11305 A的单胺氧化酶抑制特性。
Eur J Pharmacol. 1983 Oct 14;94(1-2):73-83. doi: 10.1016/0014-2999(83)90443-0.
9
Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey.松鼠猴全身给予1-甲基-4-苯基-1,2,5,6-四氢吡啶（MPTP）后的选择性黑质毒性
Brain Res. 1984 Feb 6;292(2):390-4. doi: 10.1016/0006-8993(84)90777-7.
10
Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys.帕吉林和司来吉兰可预防1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对猴子的神经毒性。
Eur J Pharmacol. 1984 Oct 30;106(1):209-10. doi: 10.1016/0014-2999(84)90700-3.
Zotero 插件