From glycosylation disorders to dolichol biosynthesis defects: a new class of metabolic diseases.
From glycosylation disorders to dolichol biosynthesis defects: a new class of metabolic diseases.
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DOI：
10.1007/s10545-011-9301-0
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发表时间：
2011-08
影响因子：
4.2
通讯作者：
Lefeber, Dirk J.
中科院分区：
文献类型：
--
作者：
Cantagrel, Vincent;Lefeber, Dirk J.
多异戊二烯醇类是存在于每个细胞中的膜脂，从古生物到高等真核生物都是保守的。最常见的形式是α-饱和聚戊烯醇或多元醇，存在于真核细胞的所有组织和大多数细胞器膜中。在N-连接蛋白糖基化的早期阶段，Dolicol作为糖前体的脂质载体具有明确的作用，N-连接蛋白糖基化是在所有真核细胞的内质网中组装的。其他糖基化过程，包括C-和O-甘露糖化、GPI-锚定生物合成和O-糖基化，也依赖于内质网中可利用的多酚-P-甘露糖和多酚-P-葡萄糖的生物合成。在没有参与糖基化的细胞隔间中普遍存在的多元醇增加了独立于这些蛋白质翻译后修饰的额外功能的可能性。多醇及其衍生物的合成和回收过程中涉及的几个步骤的分子基础尚不清楚，这阻碍了对这一方向的进一步研究。在这篇综述中，我们总结了关于苯二酚代谢物的结构和功能方面的现有知识。我们将描述在人类已知的苯二醇生物合成和循环步骤中存在缺陷的代谢紊乱，并讨论其致病机制。探索与这些疾病相关的发育、细胞和生化缺陷将有助于更好地了解这一类脂质在人类中的功能。
Polyisoprenoid alcohols are membrane lipids that are present in every cell, conserved from archaea to higher eukaryotes. The most common form, alpha-saturated polyprenol or dolichol is present in all tissues and most organelle membranes of eukaryotic cells. Dolichol has a well defined role as a lipid carrier for the glycan precursor in the early stages of N-linked protein glycosylation, which is assembled in the endoplasmic reticulum of all eukaryotic cells. Other glycosylation processes including C- and O-mannosylation, GPI-anchor biosynthesis and O-glucosylation also depend on dolichol biosynthesis via the availability of dolichol-P-mannose and dolichol-P-glucose in the ER. The ubiquity of dolichol in cellular compartments that are not involved in glycosylation raises the possibility of additional functions independent of these protein post-translational modifications. The molecular basis of several steps involved in the synthesis and the recycling of dolichol and its derivatives is still unknown, which hampers further research into this direction. In this review, we summarize the current knowledge on structural and functional aspects of dolichol metabolites. We will describe the metabolic disorders with a defect in known steps of dolichol biosynthesis and recycling in human and discuss their pathogenic mechanisms. Exploration of the developmental, cellular and biochemical defects associated with these disorders will provide a better understanding of the functions of this lipid class in human.
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DOI：
10.1073/pnas.66.1.153
发表时间：
1970-01-01
影响因子：
11.1
作者：
BEHRENS, NH;LELOIR, LF
通讯作者：
LELOIR, LF
影响因子：
4.2
作者：
EDLUND, C;SODERBERG, M;KRISTENSSON, K
通讯作者：
KRISTENSSON, K
影响因子：
3.9
作者：
D'SOUZA-SCHOREY, C;MCLACHLAN, KR;ELBEIN, AD
通讯作者：
ELBEIN, AD
影响因子：
3.9
作者：
ERICSSON, J;APPELKVIST, EL;DALLNER, G
通讯作者：
DALLNER, G
影响因子：
4.5
作者：
Belgareh-Touzé, N;Corral-Debrinski, M;Haguenauer-Tsapis, R
通讯作者：
Haguenauer-Tsapis, R