Igal R A, Coleman R A
Department of Nutrition, University of North Carolina at Chapel Hill, 27599, USA.
J Lipid Res. 1998 Jan;39(1):31-43.
Neutral lipid storage disease (NLSD) is an autosomal recessive disorder characterized by the presence of numerous lipid droplets in virtually all tissues examined. The increased cellular triacylglycerol content results from defective recycling of triacylglycerol-derived diacylglycerol to phospholipids (Igal, R. A. and R. A. Coleman. 1996. J. Biol. Chem. 271: 16644-16651). In order to determine whether de novo glycerolipid synthesis is also altered in NLSD, we compared the ability of normal human skin fibroblasts and fibroblasts from a patient with NLSD to incorporate phospholipid precursors into cell lipids. NLSD cells had increased rates of incorporation of [14C]oleic acid and [3H]glycerol into triacylglycerol and all phospholipid species except phosphatidylethanolamine. However, the cell content of each phospholipid species was similar in control and NLSD cells, indicating a higher turnover rate in NLSD cells for phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and sphingomyelin. Labeling with [14C]choline and [14C]ethanolamine confirmed the increase in the rate of phosphatidylcholine synthesis and the decreased rate of phosphatidylethanolamine synthesis through their respective CDP pathways. The activities of the major regulatory enzymes of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine biosynthesis were similar in control and NLSD cells. Taken as a whole, this study provides strong evidence for an underlying regulatory defect in NLSD that alters the rates of synthesis and degradation of the major cellular phospholipids.
中性脂质贮积病（NLSD）是一种常染色体隐性疾病，其特征是在几乎所有检查的组织中都存在大量脂滴。细胞三酰甘油含量的增加是由于三酰甘油衍生的二酰甘油向磷脂的循环利用存在缺陷（伊加尔，R.A.和R.A.科尔曼。1996年。《生物化学杂志》271:16644 - 16651）。为了确定NLSD中从头合成甘油olipid是否也发生改变，我们比较了正常人皮肤成纤维细胞和NLSD患者的成纤维细胞将磷脂前体掺入细胞脂质的能力。NLSD细胞将[14C]油酸和[3H]甘油掺入三酰甘油以及除磷脂酰乙醇胺外的所有磷脂种类的速率增加。然而，对照细胞和NLSD细胞中每种磷脂种类的细胞含量相似，这表明NLSD细胞中磷脂酰胆碱、磷脂酰肌醇、磷脂酰丝氨酸和鞘磷脂的周转率更高。用[14C]胆碱和[14C]乙醇胺标记证实了通过各自的CDP途径磷脂酰胆碱合成速率增加而磷脂酰乙醇胺合成速率降低。三酰甘油、磷脂酰胆碱和磷脂酰乙醇胺生物合成的主要调节酶的活性在对照细胞和NLSD细胞中相似。总体而言，这项研究为NLSD中存在潜在的调节缺陷提供了有力证据，该缺陷改变了主要细胞磷脂的合成和降解速率。
