Endocannabinoids and diacylglycerol kinase activity.
Endocannabinoids and diacylglycerol kinase activity.
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DOI：
10.1016/j.bbamem.2010.12.022
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
--
作者：
Gantayet, Arpita;Jegatheswaran, Januvi;Jayakumaran, Gowtham;Topham, Matthew K.;Epand, Richard M.
哺乳动物二酰甘油激酶 (DGK) 是催化二酰甘油磷酸化产生磷脂酸的酶家族。这些酶与单酰甘油的相互作用程度是本研究的重点。由于单酰基甘油和二酰基甘油之间的结构关系，人们可能期望单酰基甘油是 DGK 的底物或抑制剂。这会对脂质代谢产生一些影响。受影响的脂质代谢物之一是 2-花生四烯酰甘油 (2-AG)，它是 CB1 大麻素受体的内源配体。我们确定单甘油酯 2-AG 或 2-油酰甘油 (2-OG) 是否影响二酰甘油激酶 (DGK) 活性。我们发现 2-AG 对于 DGK 的 epsilon 或 zeta 异构体来说都是非常差的底物。此外，2-AG 是这两种 DGK 亚型的抑制剂。 2-OG 也是这两种 DGK 异构体的不良底物。作为抑制剂，2-OG 对 DGKε 的抑制作用小于 2-AG，而对于 DGKζ，这两种单酸甘油酯具有相似的抑制效力。这些结果对 DGKε 在神经元功能和癫痫中的已知作用具有影响，因为这种酶的作用将去除 1-硬脂酰-2-花生四烯酰甘油，即内源性大麻素 2-AG 的前体。
Mammalian diacylglycerol kinases (DGK) are a family of enzymes that catalyze the phosphorylation of diacylglycerol to produce phosphatidic acid. The extent of interaction of these enzymes with monoacylglycerols is the focus of the present study. Because of the structural relationship between mono- and diacylglycerols, one might expect the monoacylglycerols to be either substrates or inhibitors of DGK. This would have some consequence to lipid metabolism. One of the lipid metabolites that would be affected is 2-arachidonoyl glycerol (2-AG), which is an endogenous ligand for the CB1 cannabinoid receptor. We determined if the monoglycerides 2-AG or 2-oleoyl glycerol (2-OG) affected diacylglycerol kinase (DGK) activity. We found that 2-AG is a very poor substrate for either the epsilon or the zeta isoforms of DGK. Moreover, 2-AG is an inhibitor for both of these DGK isoforms. 2-OG is also a poor substrate for these two isoforms of DGK. As an inhibitor, 2-OG inhibits DGKε less than does 2-AG, while for DGKζ these two monoglycerides have similar inhibitory potency. These results have implications for the known role of DGKε in neuronal function and in epilepsy since the action of this enzyme will remove 1-stearoyl-2-arachidonoylglycerol, the precursor of the endocannabinoid 2-AG.
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影响因子：
2.9
作者：
Milne, Stephen B.;Ivanova, Pavlina T.;Armstrong, Michelle D.;Myers, David S.;Lubarda, Jovana;Shulga, Yulia V.;Topham, Matthew K.;Brown, H. Alex;Epand, Richard M.
通讯作者：
Epand, Richard M.
影响因子：
4.8
作者：
Han, Gil-Soo;O'Hara, Laura;Carman, George M.
通讯作者：
Carman, George M.
影响因子：
3.9
作者：
Nakane, S;Oka, S;Sugiura, T
通讯作者：
Sugiura, T
影响因子：
2.7
作者：
Oka, Saori;Arai, Shunsuke;Sugiura, Takayuki
通讯作者：
Sugiura, Takayuki
影响因子：
2.5
作者：
Rizzo, Valerio;Ferraro, Giuseppe;Sardo, Pierangelo
通讯作者：
Sardo, Pierangelo