Sphingolipid biosynthesis in man and microbes.
Sphingolipid biosynthesis in man and microbes.
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DOI：
10.1039/c8np00019k
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发表时间：
2018-09-19
影响因子：
11.9
通讯作者：
Campopiano DJ
中科院分区：
文献类型：
--
作者：
Harrison PJ;Dunn TM;Campopiano DJ
鞘脂几乎存在于生命的所有领域，在结构和信号传导中发挥着无数重要作用。这篇综述涵盖了原核生物和真核生物鞘脂生物合成酶的关键酶的结构、机制和抑制剂的最新研究亮点。一项涵盖 2018 年的新综述 鞘脂是重要的分子，尽管其历史悠久，但至今仍引起人们的兴趣。其原因是，除了在细胞膜内发挥结构作用外，它们还被证明具有对真核和原核生物体的正确功能至关重要的多种细胞信号传导功能。事实上，鞘脂失调会改变这些关键脂质的严格控制的平衡，与糖尿病、哮喘和各种神经病理学等许多疾病密切相关。鞘脂的生物发生、代谢和调节是由大量的酶、蛋白质和第二信使介导的。所有产生鞘脂的生物体似乎都有一个共同的核心途径，但最近的研究已经开始剖析重要的物种特异性差异。其中许多是最近才被发现的，并且在大多数情况下，分子和生化细节才刚刚开始出现。在经典生物化学与临床症状存在直接联系的情况下，许多制药公司开展了药物化学活动，试图提供治疗干预措施来缓解多种疾病。在适当的情况下，我们会重点关注天然产品已被用作有用工具的目标。考虑到所有这些方面，本综述涵盖了鞘脂生物合成和代谢酶的结构、机制和调节特征。
Sphingolipids are found in nearly all domains of life where they play a myriad of essential roles in structure and signalling. This review covers recent highlights from studies of the structures, mechanisms and inhibitors of key enzymes from the sphingolipid biosynthetic enzymes of prokaryotes and eukaryotes. A new review covering up to 2018 Sphingolipids are essential molecules that, despite their long history, are still stimulating interest today. The reasons for this are that, as well as playing structural roles within cell membranes, they have also been shown to perform a myriad of cell signalling functions vital to the correct function of eukaryotic and prokaryotic organisms. Indeed, sphingolipid disregulation that alters the tightly-controlled balance of these key lipids has been closely linked to a number of diseases such as diabetes, asthma and various neuropathologies. Sphingolipid biogenesis, metabolism and regulation is mediated by a large number of enzymes, proteins and second messengers. There appears to be a core pathway common to all sphingolipid-producing organisms but recent studies have begun to dissect out important, species-specific differences. Many of these have only recently been discovered and in most cases the molecular and biochemical details are only beginning to emerge. Where there is a direct link from classic biochemistry to clinical symptoms, a number a drug companies have undertaken a medicinal chemistry campaign to try to deliver a therapeutic intervention to alleviate a number of diseases. Where appropriate, we highlight targets where natural products have been exploited as useful tools. Taking all these aspects into account this review covers the structural, mechanistic and regulatory features of sphingolipid biosynthetic and metabolic enzymes.
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影响因子：
--
作者：
Beattie AE;Gupta SD;Frankova L;Kazlauskaite A;Harmon JM;Dunn TM;Campopiano DJ
通讯作者：
Campopiano DJ
影响因子：
3.9
作者：
Bertoldi, Mariarita
通讯作者：
Bertoldi, Mariarita
影响因子：
4.8
作者：
Billich, A;Bornancin, F;Baumruker, T
通讯作者：
Baumruker, T
影响因子：
3.5
作者：
Bode, Heiko;Bourquin, Florence;Hornemann, Thorsten
通讯作者：
Hornemann, Thorsten
影响因子：
2.7
作者：
Argiriadi, Maria A.;Banach, David;Harris, Christopher M.
通讯作者：
Harris, Christopher M.