Defective ABCA1 causes TGD

In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1) mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is post-translationally modified (palmitoylated and phosphorylated), predominantly a tetramer and is associated with apolipoprotein A-I (APOA1). Defects in ABCA1 can cause Tangier disease (TGD; MIM:205400 aka high density lipoprotein deficiency type 1), an autosomal recessive disorder characterised by significantly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters (Brooks-Wilson et al. 1999). Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients (Kolovou et al. 2006, Iatan et al. 2008, Iatan et al. 2012).

在ATP依赖性反应中，ATP结合盒亚家族A成员1（ABCA1）介导细胞内胆固醇向质膜细胞外面的转运。与细胞质囊泡相关的胆固醇是该反应的底物。在生理条件下，ABCA1的活性形式在翻译后进行修饰（棕榈酰化和磷酸化），主要为四聚体，并与载脂蛋白A-I（APOA1）相关联。ABCA1的缺陷可导致唐氏病（TGD；MIM:205400，亦称高密度脂蛋白缺乏症1型），这是一种常染色体隐性遗传疾病，其特征为血浆高密度脂蛋白（HDL）水平显著降低，导致胆固醇酯在组织中积累（Brooks-Wilson 等，1999年）。低HDL水平是冠状动脉心脏病（CHD）患者中最常见的生化异常之一（Kolovou 等，2006年，Iatan 等，2008年，Iatan 等，2012年）。