Topological probes of monoamine oxidases A and B in rat liver mitochondria: inhibition by TEMPO-substituted pargyline analogues and inactivation by proteolysis.
Topological probes of monoamine oxidases A and B in rat liver mitochondria: inhibition by TEMPO-substituted pargyline analogues and inactivation by proteolysis.
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DOI：
10.1021/bi101722b
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发表时间：
2011-04-05
期刊：
影响因子：
2.9
通讯作者：
Edmondson DE
中科院分区：
文献类型：
--
作者：
Wang J;Edmondson DE
TEMPO取代的帕吉林类似物在完整的酵母线粒体中差异性地抑制重组人单胺氧化酶A（MAO A）和B（MAO B），表明这些膜结合酶位于线粒体外膜的不同面上（Upadhyay，A.和Edmondson，D.E.，Biochemistry 48，3928，2009）。这种方法扩展到重组大鼠酶和大鼠肝线粒体。Meta-和对-氨基克里思帕吉林对人MAO A和MAO B表现出的差异特异性与大鼠酶的差异特异性不同。在毕赤酵母表达的或从大鼠肝脏分离的线粒体外膜制剂中，观察到大鼠MAO A和B的类似反应模式。在完整的酵母线粒体中，重组大鼠MAO B被帕吉林类似物抑制，而MAO A活性显示无抑制。完整的大鼠肝线粒体表现出与在酵母中观察到的相反的抑制模式，其中MAO A被抑制而MAO B活性不受影响。蛋白酶失活研究显示特异性，因为MAO A对胰蛋白酶敏感，而MAO B对β-胰凝乳蛋白酶敏感。在完整的线粒体制备物中，在胰蛋白酶处理下，MAO A在大鼠肝脏中容易失活，但在酵母中不失活，并且MAO B在酵母中容易被β-糜蛋白酶失活，但在大鼠肝脏中不失活。这些数据表明，在大鼠肝脏中，MAO A定位于线粒体外膜的胞质表面，而MAO B位于面向膜间隙的表面。MAO A和MAO B的不同线粒体外膜拓扑结构与其被设计为心脏保护剂或神经保护剂的药物抑制有关。
TEMPO-substituted pargyline analogues differentially inhibit recombinant human Monoamine Oxidase A (MAO A) and B (MAO B) in intact yeast mitochondria suggesting these membrane-bound enzymes are located on differing faces of the mitochondrial outer membrane (Upadhyay, A. and Edmondson, D.E., Biochemistry 48, 3928, 2009). This approach is extended to the recombinant rat enzymes and to rat liver mitochondria. The differential specificities exhibited for human MAO A and MAO B by the meta- and para-amido TEMPO pargylines are not as absolute with the rat enzymes. Similar patterns of reactivity are observed for rat MAO A and B in mitochondrial outer membrane preparations expressed in Pichia pastoris or isolated from rat liver. In intact yeast mitochondria, recombinant rat MAO B is inhibited by the pargyline analogue whereas MAO A activity shows no inhibition. Intact rat liver mitochondria exhibit an opposite inhibition pattern to that observed in yeast where MAO A is inhibited and MAO B activity is unaffected. Protease inactivation studies show specificity in that MAO A is sensitive to trypsin whereas MAO B is sensitive to β-chymotrypsin. In intact mitochondrial preparations, MAO A is readily inactivated in rat liver but not in yeast on trypsin treatment and MAO B is readily inactivated by β-chymotrypsin in yeast but not in rat liver. These data show MAO A is oriented on the cytosolic face and MAO B is situated on the surface facing the intermembrane space of the mitochondrial outer membrane in rat liver. The differential mitochondrial outer membrane topology of MAO A and MAO B is relevant to their inhibition by drugs designed to be cardio-protectants or neuro-protectants.
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影响因子：
3.5
作者：
Binda, C;Hubálek, F;Mattevi, A
通讯作者：
Mattevi, A
影响因子：
4.1
作者：
RUSSELL, SM;DAVEY, J;MAYER, RJ
通讯作者：
MAYER, RJ
影响因子：
7.3
作者：
Novaroli, Laura;Daina, Antoine;Reist, Marianne
通讯作者：
Reist, Marianne
DOI：
10.1111/j.1432-1033.1968.tb00361.x
发表时间：
1968-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
PFAFF, E;KLINGENBERG, M;VOGELL, W
通讯作者：
VOGELL, W
DOI：
10.1073/pnas.0505975102
发表时间：
2005-09-06
影响因子：
11.1
作者：
De Colibus, L;Li, M;Mattevi, A
通讯作者：
Mattevi, A