琥珀酸作为信号转递体的多方面作用因其细胞位置的不同而不同
全日制英语班Multifaceted Actions of Succinate as a Signaling Transmitter Vary with Its Cellular Locations.
行为神经科学
借贷记帐法|核心内容：
自2004年琥珀酸受体被发现以来，已有大量研究支持琥珀酸通过其受体参与多种疾病的信号传导，而且大多数研究都强调了琥珀酸的促炎作用。
考虑到琥珀酸是线粒体活动中心的中间代谢物，并考虑到其通过琥珀酰辅酶A对蛋白质琥珀酸化的潜在调节作用，有必要对琥珀酸的多方面作用进行综述，以讨论这些作用是否以及如何与琥珀酸的细胞位置有关。
从机理上讲，重要的是要考虑琥珀酸的来源，包括体细胞释放的琥珀酸，以及由微生物群产生的琥珀酸，特别是肠道微生物区系。
这两个来源对体内琥珀酸水平的贡献相当，如果体内没有更大来源的话。
继续了解琥珀酸信号在许多病理生理条件下的关键作用，无论是已知的还是未知的，都是重要的。
男警察和女警察们此外，还需要研究描述琥珀酸水平的调节，以及确定琥珀酸如何在时间和空间上引发各种类型的信号。
四级考试分数线原文摘要：
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to motherSince the identification of succinate's receptor in 2004, studies supporting the involvement of succinate signaling through its receptor in various dias have accumulated and most of the investigations have highlighted succinate's pro-inflammatory role.
Taken with the fact that succinate is an intermediate metabolite in the center of mitochondrial activity, and considering its potential regulation of protein succinylation through succinyl-coenzyme A, a review on the overall multifaceted actions of succinate to
discuss whether and how the actions relate to the cellular locations of succinate is much warranted.
Mechanistically, it is important to consider the sources of succinate, which include somatic cellular relead succinate and tho produced by the microbiome, especially the gut microbiota, which is an equivalent, if not greater contributor of succinate levels in the body.
equivalent[ɪˈkwɪvələnt]: a person or thing equal to another in value or measure or force or effect or significance etc
Continue learning the critical roles of succinate signaling, known and unknown, in many pathophysiological conditions is important.
Furthermore, studies to delineate the regulation of succinate levels and to determine how succinate elicits various types of signaling in a temporal and spatial manner are also required.
Mtabolic citrates (any salt or ester of citric acid. Salts of citric acid are ud in beverages and pharmaceuticals 柠檬酸盐; 柠檬酸酯) such as succinate and NAD+ have recently emerged as important players in various inflammatory conditions.
Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and is known to play an esntial role in adenosine triphosphate（ATP）generation in mitochondria.
In line with the extensive rearch focud on the metabolic functions of mitochondria in human pathophysiology, studies that reveal novel functions and regulatory mechanisms of succinate are growing.
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Succinate's role as a signaling transducer includes at least three levels of regulation: as an intermediate metabolite to regulate cellular metabolism and respiration, as a substrate for succinyl-coenzyme A (CoA) to conduct protein post-translational modification (PTM) via succinylation, and as a hormone-like molecule to activate succinate receptors.
作为调节细胞代谢和呼吸的中间代谢物，作为琥珀酰辅酶A (CoA)通过琥珀酸化进行蛋白质翻译后修饰(PTM)的底物，以及作为激素样分子激活琥珀酸受体。
The role of intracellular succinate as a metabolite which stabilizes hypoxia-inducible factor (HIF)-1α in respon to hypoxia, enhances interleukin-1β (IL-1β) production during inflammation in innate immune signaling and stimulates macrophage polarization has been well-characterized.
Emerging evidence indicates there is also a regulatory role of succinate in energy expenditure, weight control, and metabolic homeostasis .
Notably, succinate is one of the metabolites that is incread in the plasma in respon to exerci and up-regulates the expression of a transcriptional regulator of gluco utilization and lipid metabolism genes in skeletal muscle in vitro.
听的英文The reversible reaction of succinyl-CoA to succinate is catalyzed by succinyl-CoA syntheta (succinate thiokina).
Succinate can directly influence the level of succinyl-CoA and the lysine succinylation of proteins.
investigator
Lysine succinylation has recently been identified as a PTM that involves an addition of a succinyl group (-CO-CH2-CH2-CO2H) to a lysine residue in a protein.
Lysine succinylation extensively regulates metabolic enzyme activities in mitochondria .
It is interesting that SDH is activated by lysine succinylation （but suppresd by Itaconate），suggesting a lf-regulatory mechanism of succinate levels in mitochondria.
Extensive lysine succinylation has been found in enzymes involved in mitochondrial metabolism, including the TCA cycle, and fatty acid metabolism .
In mammalian cells, it often occurs at the same lysine residues as acetylation .
Notably, succinyl groups contain a negatively charged carboxyl group, indicating succinylation and acetylation are functionally distinct.
Indeed, SDH activity is reduced by lysine acetylation and stimulated by succinylation.
The incread lysine acetylation has been found in mesangial and tubular cells expod to high levels of gluco suggesting that acetylation reduces SDH activity causing succinate accumulation in high gluco environments.
