分子遗传缺肉碱palmitoyltransferase II的表征。
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电路研究F, Verderio E,或者是年代,Cavadini P, Finocchiaro G, Uziel G, Lamantea E, Gellera C, DiDonato年代
分子遗传缺肉碱palmitoyltransferase II的表征。
《美国国家科学院刊S a . 1992年9月15日;89(18):8429 - 33所示。
- PubMed ID
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1528846 (在PubMed]
- 文摘
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缺乏肉碱palmitoyltransferase II (CPTase II;palmitoyl-CoA:左卡尼汀O-palmitoyltransferase, EC 2.3.1.21)是一种临床异构常染色体隐性障碍的能量代谢。我们研究的分子基础CPTase二缺一个早发性患者呈现hypoketotic低血糖和心肌病。互补脱氧核糖核酸和基因组DNA分析表明,病人是纯合子突变CPTase II等位基因(称为ICV),进行三个错义突变:g - 1203——一个过渡,预测val - 368——Ile替换(V368I);c - 1992 T——过渡,预测一个参数- 631 - - - - -半胱氨酸替换(R631C);和a - 2040 - - - - - G过渡,预测了- 647 - - - - - Val替换(M647V)。家庭成员的基因组DNA分析表明,突变cosegregated疾病的家庭。然而,筛选59健康对照组证明V368I和M647V突变序列多态性等位基因频率为0.5和0.25,分别。相比之下,R631C替换中没有检测到正常22个人或在12 14 CPTase II-deficient成人患者肌肉形式。值得注意的是,2成人CPTase II-deficient患者ICV等位基因杂合的,因此建议化合物和不同的突变等位基因杂合性。 The consequences of the three mutations on enzyme activity were investigated by expressing normal and mutated CPTase II cDNAs in COS cells. The R631C substitution drastically depressed the catalytic activity of CPTase II, thus confirming that this is the crucial mutation. Interestingly, the V368I and M647V substitutions, which did not affect enzyme activity alone, exacerbated the effects of the R631C substitution. Biochemical characterization of mutant CPTase II in patient's cells showed that the mutations are associated with (i) severe reduction of Vmax (approximately 90%), (ii) normal apparent Km values, and (iii) decreased protein stability.