突变型β细胞葡萄糖激酶的结构不稳定性：对青年发病型成年糖尿病（2型）分子发病机制的影响。
Structural instability of mutant beta-cell glucokinase: implications for the molecular pathogenesis of maturity-onset diabetes of the young (type-2).
作者信息
Kesavan P, Wang L, Davis E, Cuesta A, Sweet I, Niswender K, Magnuson M A, Matschinsky F M
机构信息
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6015, USA.
出版信息
Biochem J. 1997 Feb 15;322 ( Pt 1)(Pt 1):57-63. doi: 10.1042/bj3220057.
Abstract
The catalytic function and thermal stability of wild-type and mutant recombinant human pancreatic beta-cell glucokinase was investigated. The mutants E70K and E300K, which are thought to be the cause of impaired insulin production by the pancreatic beta-cell and decreased glucose uptake by the liver of patients with maturity-onset diabetes of the young, were found to be functionally indistinguishable from the wild-type, i.e. their kcat.S0.5, inflection point and h were normal. However, these two mutants showed markedly reduced stability under a variety of test conditions. Glucokinase instability, not low enzyme catalytic activity, may be the cause of diabetes mellitus with E70K and E300K mutants.
摘要
对野生型和突变型重组人胰岛β细胞葡萄糖激酶的催化功能和热稳定性进行了研究。E70K和E300K突变体被认为是导致年轻的成年发病型糖尿病患者胰岛β细胞胰岛素分泌受损和肝脏葡萄糖摄取减少的原因，结果发现它们在功能上与野生型没有区别，即它们的kcat.S0.5、拐点和h均正常。然而，在各种测试条件下，这两个突变体的稳定性均显著降低。葡萄糖激酶不稳定，而非低酶催化活性，可能是E70K和E300K突变体所致糖尿病的病因。
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