Ceramide synthases at the centre of sphingolipid metabolism and biology.
Ceramide synthases at the centre of sphingolipid metabolism and biology.
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DOI：
10.1042/bj20111626
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Obeid LM
中科院分区：
文献类型：
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作者：
Mullen TD;Hannun YA;Obeid LM
后生动物细胞中的鞘脂代谢由众多酶、代谢物和调节模式组成的复杂互连网络组成。鞘脂代谢的核心是 CerSs（神经酰胺合酶），这是一组催化鞘氨醇碱和酰基辅酶 A 底物形成神经酰胺的酶。从代谢的角度来看，这些酶占据了独特的地位，因为它们同时调节鞘脂的从头合成和预形成鞘脂降解产生的游离鞘氨醇的回收（补救途径）。已鉴定出六种哺乳动物 CerS（CerS1–CerS6）。这些酶中的每一种都具有独特的特征，但也许最值得注意的是各个 CerS 同工型产生具有特征性酰基链分布的神经酰胺的能力。通过这种对酰基链长度的控制，并且可能以区室特异性的方式，CerS 似乎可以调节鞘脂介导的细胞和生物体生物学的多个方面。在本综述中，我们讨论了 CerS 作为鞘脂代谢关键调节因子的功能，强调了其独特的特性，并探讨了 CerS 在调节程序性细胞死亡、癌症和生物学的许多其他方面中的新兴作用。
Sphingolipid metabolism in metazoan cells consists of a complex interconnected web of numerous enzymes, metabolites and modes of regulation. At the centre of sphingolipid metabolism reside CerSs (ceramide synthases), a group of enzymes that catalyse the formation of ceramides from sphingoid base and acyl-CoA substrates. From a metabolic perspective, these enzymes occupy a unique niche in that they simultaneously regulate de novo sphingolipid synthesis and the recycling of free sphingosine produced from the degradation of pre-formed sphingolipids (salvage pathway). Six mammalian CerSs (CerS1–CerS6) have been identified. Unique characteristics have been described for each of these enzymes, but perhaps the most notable is the ability of individual CerS isoforms to produce ceramides with characteristic acyl-chain distributions. Through this control of acyl-chain length and perhaps in a compartment-specific manner, CerSs appear to regulate multiple aspects of sphingolipid-mediated cell and organismal biology. In the present review, we discuss the function of CerSs as critical regulators of sphingolipid metabolism, highlight their unique characteristics and explore the emerging roles of CerSs in regulating programmed cell death, cancer and many other aspects of biology.