Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity.
Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity.
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DOI：
10.1016/j.plefa.2020.102175
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Ellis JM
中科院分区：
文献类型：
--
作者：
Fernandez RF;Ellis JM
每个细胞类型都是由其独特的形态、表型、分子和脂质组学特征来定义的。维持细胞特异性脂质组谱的重要性可以通过脂质组改变直接导致的许多疾病、失调和功能失调结果来例证。因此，调节细胞脂质组多样性的机制在维持基本的生物学功能中起着重要作用。大脑是一个特别富含磷脂的器官，磷脂是细胞膜的主要成分。脑膜的磷脂酰基链谱相当多样化，部分原因是细胞的高度异质性。这些膜及其磷脂的酰基链组成受到高度调节，但赋予这种严格调节的机制尚不完全清楚。一种被称为酰基辅酶A合成酶（ACSs）的酶家族处于顶峰阶段，可以影响细胞酰基链的选择和随后的代谢通量。ACSs通过将辅酶a连接到脂肪酸上来完成细胞脂肪酸代谢的初始反应，该反应将脂肪酸困在细胞内并激活其代谢。ACS酶家族庞大而多样，由25-26个非冗余的家族成员组成，每个家族成员在细胞类型和细胞类型中都有独特的分布，并有不同的脂肪酸底物偏好。因此，ACSs以细胞类型依赖的方式赋予细胞内关键的脂肪酸选择步骤，提供酰基辅酶a片段，作为磷脂合成和重塑的重要前体，因此作为细胞膜酰基链组成多样性的关键调节剂。在这里，我们将讨论个体ACSs对脑脂质代谢的贡献如何才刚刚开始阐明，并讨论ACSs如何差异调节脑脂质组多样性的可能性。
Each individual cell-type is defined by its distinct morphology, phenotype, molecular and lipidomic profile. The importance of maintaining cell-specific lipidomic profiles is exemplified by the numerous diseases, disorders, and dysfunctional outcomes that occur as a direct result of altered lipidome. Therefore, the mechanisms regulating cellular lipidome diversity play a role in maintaining essential biological functions. The brain is an organ particularly rich in phospholipids, the main constituents of cellular membranes. The phospholipid acyl-chain profile of membranes in the brain is rather diverse due in part to the high degree of cellular heterogeneity. These membranes and the acyl-chain composition of their phospholipids are highly regulated, but the mechanisms that confer this tight regulation are incompletely understood. A family of enzymes called acyl-CoA synthetases (ACSs) stands at a pinnacle step allowing influence over cellular acyl-chain selection and subsequent metabolic flux. ACSs perform the initial reaction for cellular fatty acid metabolism by ligating a Coenzyme A to a fatty acid which both traps a fatty acid within a cell and activates it for metabolism. The ACS family of enzymes is large and diverse consisting of 25–26 family members that are nonredundant, each with unique distribution across and within cell types, and differential fatty acid substrate preferences. Thus, ACSs confer a critical intracellular fatty acid selecting step in a cell-type dependent manner providing acyl-CoA moieties that serve as essential precursors for phospholipid synthesis and remodeling, and therefore serve as a key regulator of cellular membrane acyl-chain compositional diversity. Here we will discuss how the contribution of individual ACSs towards brain lipid metabolism has only just begun to be elucidated and discuss the possibilities for how ACSs may differentially regulate brain lipidomic diversity.
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影响因子：
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作者：
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DOI：
10.1038/nri.2015.4
发表时间：
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期刊：
Nature reviews. Immunology
影响因子：
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作者：
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影响因子：
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作者：
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