THE NATURE OF THE INHIBITION OF RAT-LIVER MONOAMINE-OXIDASE TYPE-A AND TYPE-B BY THE ACETYLENIC INHIBITORS CLORGYLINE, L-DEPRENYL AND PARGYLINE
THE NATURE OF THE INHIBITION OF RAT-LIVER MONOAMINE-OXIDASE TYPE-A AND TYPE-B BY THE ACETYLENIC INHIBITORS CLORGYLINE, L-DEPRENYL AND PARGYLINE
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DOI：
10.1016/0006-2952(82)90575-5
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发表时间：
1982-01-01
影响因子：
5.8
通讯作者：
TIPTON, KF
中科院分区：
文献类型：
--
作者：
FOWLER, CJ;MANTLE, TJ;TIPTON, KF
氯吉兰，l-丙炔苯丙胺和帕吉林抑制大鼠肝线粒体氧化酶的动力学是一致的机制，即在热力学平衡的条件下，抑制剂和酶活性位点之间的可逆相互作用，随后由共价结合的酶-抑制剂加合物的时间依赖性形成。氯吉兰和单胺氧化酶A之间可逆相互作用的Ki [抑制常数]值为λ。比对酶的B-形式的低1000倍，并且该差异足以解释由该化合物引起的抑制的大部分但不是全部的选择性。单胺氧化酶B-选择性抑制剂1-丙炔苯丙胺对该酶形式的Ki值仅为比A型低40倍B-型的不可逆加合物的形成速率比A-型快得多，这对该化合物的选择性做出了主要贡献。帕吉林对单胺氧化酶B的Ki值仅比对A型的Ki值低8倍，在这种情况下，酶-抑制剂加合物的形成速率相似。这些结果的意义进行了讨论的单胺氧化酶的选择性抑制。
The kinetics of inhibition of rat liver mitochondrial oxidase by clorgyline, l-deprenyl and pargyline are consistent with a mechanism whereby a reversible interaction between the inhibitor and the enzyme active site under conditions of thermodynamic equilibrium is followed by a time-dependent formation of the covalently bound enzyme-inhibitor adduct. The Ki [inhibition constant] value for the reversible interaction between clorgyline and monoamine oxidase A is .apprx. 1000 times lower than that towards the B-form of the enzyme, and this difference is sufficient to account for most, but not all, of the selectivity of the inhibition caused by this compound. The Ki value of the monoamine oxidase B-selective inhibitor l-deprenyl towards that form of the enzyme is only .apprx. at 40-fold lower than that towards the A-form. The rate of formation of the irreversible adduct is considerably faster for the B-form than for the A-form and this makes a major contribution to the selectivity of this compound. Pargyline shows a Ki value towards monoamine oxidase B that is only 8 times lower than that towards the A-form, and in this case the rates of formation of the enzyme-inhibitor adducts are similar. The significance of these results are discussed in terms of the selective inhibition of monoamine oxidase.