Kwiterovich P O, Motevalli M, Miller M, Bachorik P S, Kafonek S D, Chatterjee S, Beaty T, Virgil D
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Clin Chem. 1991 Mar;37(3):317-26.
Hyperapobetalipoproteinemia (hyperapoB), a familial lipoprotein disorder characterized by an increase in small, dense, low-density lipoprotein (LDL) particles, is strongly associated with coronary artery disease. There are two metabolic defects in hyperapoB: an increased synthesis of a very-low-density lipoprotein in liver, resulting in an overproduction of LDL, and a delayed clearance of post-prandial triglyceride and free fatty acids. To date, defects in the apolipoprotein B gene do not appear to explain the hyperapoB phenotype. Defect(s) in the uptake or intracellular metabolism of free fatty acids have been found in cells from hyperapoB patients. Three basic proteins (BPs)--BP I (Mr 14,000, pI 9.10), BP II (Mr 27,500, pI 8.48), and BP III (Mr 55,000, pI 8.73)--were isolated from normal human serum. Compared with normal fibroblasts, cultured hyperapoB fibroblasts incubated with BP I, which appears to be the same protein as acylation-stimulating protein (ASP), showed 50% less stimulation of triglyceride acylation and cholesterol esterification, whereas BP II markedly stimulated cholesteryl ester formation, and BP III caused no difference in response vs normal fibroblasts. However, in cultured normal human monocyte macrophages, BP III, but not BP I or BP II, stimulated cholesteryl esterification two- to threefold. BP I, BP II, and BP III may provide new insights into normal metabolism of lipids, lipoproteins, and free fatty acids and the pathophysiology of hyperapoB.
高载脂蛋白B血症（高apoB）是一种家族性脂蛋白紊乱疾病，其特征是小而致密的低密度脂蛋白（LDL）颗粒增加，与冠状动脉疾病密切相关。高apoB存在两种代谢缺陷：肝脏中极低密度脂蛋白合成增加，导致LDL产生过多；餐后甘油三酯和游离脂肪酸清除延迟。迄今为止，载脂蛋白B基因缺陷似乎无法解释高apoB表型。在高apoB患者的细胞中发现了游离脂肪酸摄取或细胞内代谢的缺陷。从正常人血清中分离出三种碱性蛋白（BP）——BP I（分子量14,000，等电点9.10）、BP II（分子量27,500，等电点8.48）和BP III（分子量55,000，等电点8.73）。与正常成纤维细胞相比，用BP I（似乎与酰化刺激蛋白（ASP）是同一种蛋白）孵育的培养高apoB成纤维细胞，甘油三酯酰化和胆固醇酯化的刺激作用降低了50%，而BP II显著刺激胆固醇酯形成，BP III与正常成纤维细胞相比反应无差异。然而，在培养的正常人单核巨噬细胞中，BP III而非BP I或BP II刺激胆固醇酯化增加了两到三倍。BP I、BP II和BP III可能为脂质、脂蛋白和游离脂肪酸的正常代谢以及高apoB的病理生理学提供新的见解。
