Stein O, Oette K, Hollander G, Dabach Y, Ben-Naim M, Stein Y
Department of Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Biochim Biophys Acta. 1989 Jun 8;1003(2):175-82. doi: 10.1016/0005-2760(89)90252-x.
The metabolism of sphingomyelins and ceramides with defined labeled fatty acids was compared after injection in vivo or incubation with cultured cells. The liver was the major site of uptake of sphingomyelins and ceramides with 18:2 or 16:0 fatty acids, but with both sphingolipids a higher recovery of radioactivity was found with 16:0 species. The distribution of radioactivity among liver lipids showed that 1.5 h after injection of 18:2 sphingomyelin, only 21% of the label was found as sphingomyelin, and this value was 37% in the case of 16:0 sphingomyelin. There was a very marked difference in the metabolism of 18:2 and 16:0 ceramides. After injection of 18:2 ceramide only 14% of the radioactivity was recovered as sphingomyelin, and this value was more than 50% with 16:0 ceramide. [14C]18:2 ceramide was converted also to glucoceramide and hydrolyzed more extensively than 16:0 ceramide. These observations were extended to sphingomyelins and ceramides with other fatty acids, using Hep-G2 cells in culture. Significantly more radioactivity was recovered as labeled sphingomyelin after incubation with 16:0, 18:0, 20:0 and 24:0 sphingomyelins than with 18:1 and 18:2 sphingomyelins, while more labeled phosphatidylcholine and phosphatidylethanolamine were found with the unsaturated sphingomyelins. In analogy to the findings in vivo, in the Hep-G2 cells more 16:0, 18:0 and 24:0 ceramides were converted to sphingomyelin than 18:1 or 18:2 ceramides. These differences were also seen with cultured macrophages, in which a more marked reutilization for sphingomyelin formation was found with the saturated ceramide series. The sphingomyelin liposomes were tested also for their capacity to mobilize cholesterol, and a rise in plasma unesterified cholesterol occurred after injection of 18:2 sphingomyelin. Marked enhancement of cholesterol efflux from cholesterol ester-loaded macrophages was also seen with 18:1 and 18:2, 20:0 sphingomyelin in the presence of delipidated high-density lipoprotein. The present results demonstrate that the metabolic fate of sphingolipids is related to their fatty acid composition. While ceramides with saturated fatty acids are predominantly reutilized for sphingomyelin formation, those with unsaturated fatty acids undergo probably more rapid hydrolysis with liberation of fatty acids and channeling into glycerolipids.
在体内注射或与培养细胞孵育后，对含有特定标记脂肪酸的鞘磷脂和神经酰胺的代谢进行了比较。肝脏是摄取含有18:2或16:0脂肪酸的鞘磷脂和神经酰胺的主要部位，但对于这两种鞘脂，16:0种类的放射性回收率更高。肝脏脂质中放射性的分布表明，注射18:2鞘磷脂1.5小时后，仅21%的标记物以鞘磷脂形式存在，而对于16:0鞘磷脂，该值为37%。18:2和16:0神经酰胺的代谢存在非常显著的差异。注射18:2神经酰胺后，仅14%的放射性以鞘磷脂形式回收，而对于16:0神经酰胺，该值超过50%。[14C]18:2神经酰胺也转化为葡萄糖神经酰胺，并且比16:0神经酰胺水解得更广泛。使用培养的Hep-G2细胞，这些观察结果扩展到含有其他脂肪酸的鞘磷脂和神经酰胺。与18:1和18:2鞘磷脂孵育后相比，与16:0、18:0、20:0和24:0鞘磷脂孵育后，作为标记鞘磷脂回收的放射性显著更多，而不饱和鞘磷脂中发现更多标记的磷脂酰胆碱和磷脂酰乙醇胺。与体内研究结果类似，在Hep-G2细胞中，16:0、18:0和24:0神经酰胺比18:1或18:2神经酰胺更多地转化为鞘磷脂。在培养的巨噬细胞中也观察到了这些差异，在饱和神经酰胺系列中发现了更显著的用于鞘磷脂形成的再利用。还测试了鞘磷脂脂质体动员胆固醇的能力，注射18:2鞘磷脂后血浆未酯化胆固醇升高。在脱脂高密度脂蛋白存在的情况下，18:1、18:2、20:0鞘磷脂也显著增强了胆固醇酯负载巨噬细胞的胆固醇流出。目前的结果表明，鞘脂的代谢命运与其脂肪酸组成有关。虽然含有饱和脂肪酸的神经酰胺主要重新用于鞘磷脂的形成，但含有不饱和脂肪酸的神经酰胺可能经历更快的水解，释放脂肪酸并进入甘油脂质。
