HDL 重塑
中文名称
通路描述
HDL（高密度脂蛋白）颗粒在胆固醇的逆向转运中发挥核心作用，即胆固醇从除肝脏以外的组织返回肝脏，转化为胆汁酸并排出体外，同时为肾上腺和性腺等组织提供合成类固醇激素的原料（Tall et al. 2008）。ABCG1 介导细胞内胆固醇向细胞外质膜表面移动，使其可被循环 HDL 接触（Vaughan & Oram 2005）。球形（成熟）HDL 颗粒可从细胞膜获取额外的游离胆固醇（CHOL）和磷脂（PL）。在 HDL 表面，脂酰转移酶（LCAT）与 HDL 颗粒紧密结合，并在 apoA-I 激活下催化胆固醇与磷脂酰胆碱反应，生成长链脂肪酸酯化的胆固醇和 2-磷脂酰胆碱。疏水的胆固醇酯产物与 HDL 颗粒紧密结合，而 2-磷脂酰胆碱产物被释放。Torcetrapib 与 CETP 分子及球形 HDL 颗粒结合形成稳定复合物，从而捕获 CETP 并抑制 HDL 与 LDL 之间的 CETP 介导的脂质转移（Clark et al. 2006）。球形 HDL 颗粒可结合 apoC-II、apoC-III 和 apoE 蛋白。
英文描述
HDL remodeling HDL (high-density lipoprotein) particles play a central role in the reverse transport of cholesterol, the process by which cholesterol in tissues other than the liver is returned to the liver for conversion to bile salts and excretion from the body and provided to tissues such as the adrenals and gonads for steroid hormone synthesis (Tall et al. 2008).
ABCG1 mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane where it is accessible to circulating HDL (Vaughan & Oram 2005). Spherical (mature) HDL particles can acquire additional molecules of free cholesterol (CHOL) and phospholipid (PL) from cell membranes.
At the HDL surface, LCAT (lecithin-cholesterol acyltransferase) associates strongly with HDL particles and, activated by apoA-I, catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine. The hydrophobic cholesterol ester reaction product is strongly associated with the HDL particle while the 2-lysophosphatidylcholine product is released. Torcetrapib associates with a molecule of CETP and a spherical HDL particle to form a stable complex, thus trapping CETP and inhibiting CETP-mediated lipid transfer between HDL and LDL (Clark et al. 2006).
Spherical HDL particles can bind apoC-II, apoC-III and and apoE proteins.
ABCG1 mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane where it is accessible to circulating HDL (Vaughan & Oram 2005). Spherical (mature) HDL particles can acquire additional molecules of free cholesterol (CHOL) and phospholipid (PL) from cell membranes.
At the HDL surface, LCAT (lecithin-cholesterol acyltransferase) associates strongly with HDL particles and, activated by apoA-I, catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine. The hydrophobic cholesterol ester reaction product is strongly associated with the HDL particle while the 2-lysophosphatidylcholine product is released. Torcetrapib associates with a molecule of CETP and a spherical HDL particle to form a stable complex, thus trapping CETP and inhibiting CETP-mediated lipid transfer between HDL and LDL (Clark et al. 2006).
Spherical HDL particles can bind apoC-II, apoC-III and and apoE proteins.
所含基因
10 个基因