溶酶体钴胺素转运的研究进展:cblF 病的启示。

Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease.

机构信息

Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany.

出版信息

J Mol Med (Berl). 2010 May;88(5):459-66. doi: 10.1007/s00109-010-0601-x. Epub 2010 Feb 20.

Abstract

Vitamin B(12) (cobalamin) is essential in animals and humans for metabolism of methylmalonic acid, for the remethylation of homocysteine to methionine and, consequently, for all S-adenosylmethionine-dependent methylation reactions, including DNA synthesis. In man, cobalamin deficiency leads to anemia and neurologic and cognitive impairment. In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes and cannot be converted to cofactors for mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase. Recent work has shown that this defect is caused by mutations in the lysosomal membrane protein LMBD1, which shows significant homology to lipocalin membrane receptors, thereby indicating that LMBD1 is a lysosomal membrane exporter for cobalamin.

摘要

维生素 B(12)(钴胺素)对动物和人类的代谢至关重要,它可以将甲基丙二酸转化为同型半胱氨酸,从而将其重新甲基化为蛋氨酸,进而促进所有 S-腺苷甲硫氨酸依赖性甲基化反应,包括 DNA 合成。在人类中,钴胺素缺乏会导致贫血以及神经和认知功能障碍。在 cblF 型维生素 B(12)代谢的先天性遗传缺陷中,游离的维生素在溶酶体中积累,无法转化为线粒体甲基丙二酰辅酶 A 变位酶和细胞质蛋氨酸合酶的辅助因子。最近的研究表明,这种缺陷是由溶酶体膜蛋白 LMBD1 的突变引起的,该蛋白与脂联素膜受体具有显著的同源性,表明 LMBD1 是钴胺素的溶酶体膜外排蛋白。

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