Stereochemistry of Endogenous Palmitic Acid Ester of 9-Hydroxystearic Acid and Relevance of Absolute Configuration to Regulation.
Stereochemistry of Endogenous Palmitic Acid Ester of 9-Hydroxystearic Acid and Relevance of Absolute Configuration to Regulation.
复制标题
9-羟基甲酸的内源性棕榈酸酯的立体化学以及绝对构型与调节的相关性。
DOI：
10.1021/jacs.7b01269
复制
发表时间：
2017-04-05
影响因子：
15
通讯作者：
Siegel D
中科院分区：
文献类型：
--
作者：
Nelson AT;Kolar MJ;Chu Q;Syed I;Kahn BB;Saghatelian A;Siegel D
脂质在细胞和生物体的结构、能量学和信号传导中起着重要作用。最近发现的具有抗糖尿病和抗炎活性的脂质羟基脂肪酸酯（FAHFAs）表明，我们对脂质组的组成和脂质功能的认识是不完整的。合成和测试FAHFAs的能力对于阐明这些脂质的作用至关重要，但这些研究是在外消旋混合物中进行的，而立体化学的作用仍未被探索。本文合成了9-羟基硬脂酸R-和S-棕榈酸酯（R-9- pahsa, S-9- pahsa）。高对映体富集的pahsa使得液相色谱-质谱（LC-MS）方法得以发展，以分离和定量R-和S-9-PAHSA，该方法鉴定了R-9- pahsa是主要的立体异构体，积聚在转基因小鼠的脂肪组织中，其中首次发现了FAHFAs。此外，对9-PAHSA生物合成和降解的生化分析表明，产生PAHSA的酶和途径具有立体特异性，细胞系倾向于产生R-9-PAHSA和羧基酯脂肪酶（CEL），一种PAHSA降解酶，选择性地水解S-9-PAHSA。这些研究强调了立体化学在pahsa的产生和降解中的作用，并确定了脂肪组织中9-PAHSA的内源性立体化学。这些信息将有助于确定和表征PAHSA生物合成的途径，而获得对映纯PAHSA将阐明立体化学在PAHSA活性和体内代谢中的作用。
Lipids have fundamental roles in the structure, energetics, and signaling of cells and organisms. The recent discovery of fatty acid esters of hydroxy fatty acids (FAHFAs), lipids with potent anti-diabetic and anti-inflammatory activities, indicates that our understanding of the composition of lipidome and the function of lipids is incomplete. The ability to synthesize and test FAHFAs was critical in elucidating the roles of these lipids, but these studies were performed with racemic mixtures, and the role of stereochemistry remains unexplored. Here, we synthesized the R- and S- palmitic acid ester of 9-hydroxystearic acid (R-9-PAHSA, S-9-PAHSA). Access to highly enantioenriched PAHSAs enabled the development of a liquid chromatography-mass spectrometry (LC-MS) method to separate and quantify R- and S-9-PAHSA, and this approach identified R-9-PAHSA as the predominant stereoisomer that accumulates in adipose tissues from transgenic mice where FAHFAs were first discovered. Furthermore, biochemical analysis of 9-PAHSA biosynthesis and degradation indicate that the enzymes and pathways for PAHSA production are stereospecific, with cell lines favoring the production of R-9-PAHSA and carboxyl ester lipase (CEL), a PAHSA degradative enzyme, selectively hydrolyzing S-9-PAHSA. These studies highlight the role of stereochemistry in the production and degradation of PAHSAs and define the endogenous stereochemistry of 9-PAHSA in adipose tissue. This information will be useful in the identification and characterization of the pathway responsible for PAHSA biosynthesis, and access to enantiopure PAHSAs will elucidate the role of stereochemistry in PAHSA activity and metabolism in vivo.
登录
查看更多内容
影响因子：
7.7
作者：
Kuda, Ondrej;Brezinova, Marie;Kopecky, Jan
通讯作者：
Kopecky, Jan
影响因子：
--
作者：
Ebert, Cynthia;Felluga, Fulvia;Masotti, Lanfranco
通讯作者：
Masotti, Lanfranco
DOI：
10.1152/ajpendo.1995.268.5.e956
发表时间：
1995-05-01
影响因子：
5.1
作者：
TOZZO, E;SHEPHERD, PR;KAHN, BB
通讯作者：
KAHN, BB
影响因子：
64.8
作者：
Herman, Mark A.;Peroni, Odile D.;Villoria, Jorge;Schoen, Michael R.;Abumrad, Nada A.;Blueher, Matthias;Klein, Samuel;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
14.8
作者：
Zhang T;Chen S;Syed I;Ståhlman M;Kolar MJ;Homan EA;Chu Q;Smith U;Borén J;Kahn BB;Saghatelian A
通讯作者：
Saghatelian A