A kinetic perspective on the peculiarity of aldose reductase.
A kinetic perspective on the peculiarity of aldose reductase.
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关于醛糖还原酶特性的动力学观点。
DOI：
10.1007/978-1-4684-5901-2_24
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发表时间：
1991
影响因子：
--
通讯作者：
Grimshaw,CE
中科院分区：
文献类型：
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作者：
Grimshaw,CE
由醛糖还原酶（ALR 2; alditol：NADP+1-氧化还原酶; EC 1.1.1.21）催化的D-葡萄糖还原为D-山梨糖醇与眼、肾和神经系统的糖尿病并发症的发病机制有关（Dvornik，1987; Kador，1988），因此，为了了解这种酶在体外和体内的功能，已经进行了大量的研究工作。然而，由于这种单体氧化还原酶的特殊性质，理解ALR 2催化的机理细节被证明是相当困难的。特别地，ALR 2的动力学性质一直是有争议的主题，其中关于Michaelis-Menten型动力学的报道相互矛盾（Boghosian & McGuinness，1979; Werechton等人，1982; Branlant等人，一九八二年; Cromlish & Flynn，1983 a，B; Morjana & Flynn，1989）或显示核苷酸和醛底物的明显负协同性的非线性双倒数图（Sheaff & Doughty，1976;霍夫曼等人，1980; Daly和Mantle，1982; Conrad和Doughty，1982; Haider和Crabbe，1984; Srivastava等人，1985; Poulsom，1986）。此外，已经报道了催化活性和对各种醛糖还原酶抑制剂（ARI）抑制的敏感性的变化，其取决于测定的底物和酶的纯化状态（Kador等人，1983; Maragoudakis等人，1984; Cromlish & Flynn，1985; Poulsom，1987）。最近对牛肾ALR 2的研究为理解这种相当独特的酶的特殊性质提供了理论基础。
The reduction ofD-glucose toD-sorbitol catalyzed by aldose reductase (ALR2; alditol:NADP+1-oxidoreductase; EC 1.1.1.21) has been implicated in the pathogenesis of diabetic complications of the eye, kidney, and nervous system (Dvornik, 1987; Kador, 1988), and as a result, much research effort has been expended in order to understand the function of this enzyme bothin vitroandin vivo. Understanding the mechanistic details of ALR2 catalysis has, however, proven to be rather difficult due to the peculiar character of this monomeric oxidoreductase. In particular, the kinetic properties of ALR2 have been a subject of controversy, with conflicting reports of either Michaelis-Menten type kinetics (Boghosian & McGuinness, 1979; Wermuth et al., 1982; Branlant et al., 1982; Cromlish & Flynn, 1983a,b; Morjana & Flynn, 1989) or nonlinear double-reciprocal plots displaying apparent negative cooperativity for the nucleotide and aldehyde substrate (Sheaff & Doughty, 1976; Hoffman et al., 1980; Daly & Mantle, 1982; Conrad & Doughty, 1982; Haider & Crabbe, 1984; Srivastava et al., 1985; Poulsom, 1986). In addition, changes in catalytic activity and in the susceptibility to inhibition by various aldose reductase inhibitors (ARI) have been reported that are dependent on the substrate assayed and on the purification state of the enzyme (Kador et al., 1983; Maragoudakis et al., 1984; Cromlish & Flynn, 1985; Poulsom, 1987). Recent studies of bovine kidney ALR2 provide a rationale for understanding the peculiar properties of this rather unique enzyme.