Teruya J, Cluette-Brown J, Szczepiorkowski Z M, Laposata M
Department of Pathology, Massachusetts General Hospital, Boston, USA.
J Lipid Res. 1995 Feb;36(2):266-76.
Fatty acids are transported to cells from a variety of different moieties in the plasma. In this study, using oleate and human umbilical vein endothelial cells, we asked whether the vehicle that delivers fatty acid to cells has an influence on its metabolism upon its incorporation into the cell. For oleate vehicles, we compared free oleate bound to albumin with oleate in low density lipoprotein (LDL) which was delipidated and reconstituted with either radiolabeled triolein or cholesteryl oleate. Using approximately physiologic concentrations of LDL and free oleate, we demonstrated by three lines of evidence unique patterns of cellular oleate metabolism for oleate delivered as triolein within LDL, for oleate delivered as cholesteryl oleate within LDL, and for oleate delivered as free oleate bound to albumin. In fact, the difference was most marked between cholesteryl oleate and triolein, even though the oleate in cholesteryl oleate and triolein was delivered in identically reconstituted LDL particles, which were presumably incorporated into the cells and degraded in lysosomes in a similar fashion. First, we demonstrated that oleate delivered as free oleate or as triolein in reconstituted LDL was desaturated and elongated to fatty acid metabolites, but cholesteryl oleate in reconstituted LDL was not similarly metabolized. The elongated and desaturated metabolites of oleate were preferentially esterified in cellular triglyceride when oleate was delivered as free oleate, but they were preferentially esterified in phospholipids when oleate was delivered as triolein in LDL. Second, we observed that there was a difference in the distribution of oleate among phospholipids when oleate was delivered as cholesteryl oleate in reconstituted LDL versus triolein in reconstituted LDL. When the oleate was delivered as triolein in reconstituted LDL, there was greater esterification in diacyl phosphatidylethanolamine, in phosphatidylserine, and in phosphatidylinositol. When oleate was delivered as cholesteryl oleate in reconstituted LDL, there was greater esterification in diacyl phosphatidylcholine. Third, there was a marked preference for oleate delivered from triolein in LDL over cholesteryl oleate in LDL for esterification into the sn-1 position of plasmalogens as a vinyl ether-linked fatty acid. These data indicate that mode of transport of fatty acid to cells influences fatty acid metabolism upon its incorporation into the cell, even when the fatty acid is delivered from the core of the same lipoprotein.
脂肪酸从血浆中的各种不同部分转运至细胞。在本研究中，我们使用油酸和人脐静脉内皮细胞，探究输送脂肪酸至细胞的载体在脂肪酸进入细胞后是否会对其代谢产生影响。对于油酸载体，我们将与白蛋白结合的游离油酸与低密度脂蛋白（LDL）中的油酸进行了比较，该低密度脂蛋白经脱脂处理后用放射性标记的三油精或胆固醇油酸酯进行了重构。使用大约生理浓度的LDL和游离油酸，我们通过三条证据表明，对于以三油精形式在LDL中输送的油酸、以胆固醇油酸酯形式在LDL中输送的油酸以及以与白蛋白结合的游离油酸形式输送的油酸，细胞油酸代谢具有独特模式。事实上，胆固醇油酸酯和三油精之间的差异最为显著，尽管胆固醇油酸酯和三油精中的油酸是以相同重构的LDL颗粒输送的，这些颗粒可能以类似方式被细胞摄取并在溶酶体中降解。首先，我们证明以游离油酸或三油精形式在重构LDL中输送的油酸会去饱和并延长为脂肪酸代谢产物，但重构LDL中的胆固醇油酸酯不会以类似方式代谢。当油酸以游离油酸形式输送时，油酸的延长和去饱和代谢产物优先酯化到细胞甘油三酯中，但当油酸以三油精形式在LDL中输送时，它们优先酯化到磷脂中。其次，我们观察到当油酸以胆固醇油酸酯形式在重构LDL中输送与以三油精形式在重构LDL中输送时，油酸在磷脂中的分布存在差异。当油酸以三油精形式在重构LDL中输送时，在二酰基磷脂酰乙醇胺、磷脂酰丝氨酸和磷脂酰肌醇中的酯化作用更强。当油酸以胆固醇油酸酯形式在重构LDL中输送时，在二酰基磷脂酰胆碱中的酯化作用更强。第三，与LDL中的胆固醇油酸酯相比，LDL中的三油精输送的油酸作为乙烯基醚连接的脂肪酸酯化到缩醛磷脂的sn-1位置的偏好明显更高。这些数据表明，脂肪酸向细胞的转运方式在脂肪酸进入细胞后会影响脂肪酸代谢，即使脂肪酸是从同一脂蛋白的核心输送的。
