纯合子MCEE无义突变的基因和核抑制methylmalonyl-CoA差向异构酶表达:小说引起的轻度methylmalonic酸尿。

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隆戈多布森厘米,分级,N,吴X,勒克莱尔D, Lerner-Ellis J, Lemieux M, Belair C,沃特金斯D, Rosenblatt DS,砾石RA

纯合子MCEE无义突变的基因和核抑制methylmalonyl-CoA差向异构酶表达:小说引起的轻度methylmalonic酸尿。

摩尔麝猫金属底座。2006年8月,88(4):327 - 33所示。2006年5月11日Epub。

PubMed ID

16697227 (在PubMed

]

文摘

Methylmalonyl-CoA差向异构酶(MCE)催化D -和L-methylmalonyl-CoA途径的互变现象负责降解支链氨基酸,脂肪酸链长,和其他代谢产物。尽管代谢紊乱的发生在酶步骤发生立即MCE (propionyl-CoA羧化酶)的上游和下游的多国评价(adenosylcobalamin-dependent methylmalonyl-CoA变位酶),没有描述致病突变影响多国评价本身。病人曾认定为属于cblA互补组维生素B12障碍但缺乏影响基因的突变,MMAA, MCEE基因的突变检测。患者的成纤维细胞的正常水平相比adenosylcobalamin控制,而其他cblA细胞系通常降低了代数余子式的水平。这个病人有一个温和的形式,methylmalonic酸尿比通常cblA患者中观察到。病人被发现是一个c的纯合子。139 c > T (p.R47X)突变MCEE通过序列分析证实了限制PCR产品的消化。一个兄弟,也有轻度methylmalonic酸尿,是纯合子突变。父母和另一个兄弟是杂合的。附近的一个插入多态性,c。41-160_161insT, heterozygous in both parents, showed the wild-type configuration on the mutant alleles. To assess the impact of isolated MCE deficiency in cultured cells, HeLa cells were transfected with a selectable vector containing MCEE-specific small interfering RNA (siRNA) to suppress gene expression. The reduced level of MCEE mRNA resulted in the reduction of [14C]-propionate incorporation into cellular macromolecules. However, siRNA only led to a small reduction in pathway activity, suggesting that previously postulated non-enzymatic conversion of D- to L-methylmalonyl-CoA may contribute to some flux through the pathway. We conclude that the patient's MCEE defect was responsible for the mild methylmalonic aciduria, confirming a partial requirement for the enzymatic activity in humans.

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药物靶点

药物	目标	类	生物	药理作用	行动
维生素b12	Methylmalonic酸尿蛋白类型,线粒体	蛋白质	人类	未知的	粘结剂	细节