Hahn S E, Goldberg D M
Department of Clinical Biochemistry, University of Toronto, Banting Institute, Ontario, Canada.
J Clin Lab Anal. 1995;9(6):431-49. doi: 10.1002/jcla.1860090616.
The concentration of apo B is an important risk factor for atherosclerosis, and thus its reduction is associated with a reduction in CHD mortality. In order to reduce apo B concentrations effectively, we must understand how plasma apo B concentration is regulated. Apo B is synthesized, assembled, and secreted by the liver, controlling this process will reduce the number of particles that eventually enter the plasma compartment. The assembly of apo B into a VLDL particle is a complex process which occurs through several stages: peptide synthesis, translocation, accumulation of lipid, and transport through the secretory pathway. Multiple control points regulate the synthesis and secretion of apolipoproteins. Modulation of transcription, translation and intracellular degradation represent independent regulatory mechanisms. The ability of the lipoprotein to bind cotranslationally to lipid appears to be crucial to the formation of a secreted particle. This process may be regulated solely by MTP, or may be modified by the activity of the lipid-synthesizing enzymes. A great deal of evidence supports the role of TG and CE synthesis, although the relative importance of these two lipids is a source of major controversy. In summary, all the lipoprotein components can be limiting for apo B and VLDL synthesis when their availability is substantially decreased. The rate-limiting component in vivo has still not been identified. By understanding how lipoprotein synthesis and assembly are regulated, it should become possible to design new ways of altering these processes in a beneficial manner.
载脂蛋白B的浓度是动脉粥样硬化的一个重要风险因素，因此降低其浓度与冠心病死亡率的降低相关。为了有效降低载脂蛋白B的浓度，我们必须了解血浆中载脂蛋白B的浓度是如何被调节的。载脂蛋白B由肝脏合成、组装并分泌，控制这一过程将减少最终进入血浆池的颗粒数量。载脂蛋白B组装成极低密度脂蛋白颗粒是一个复杂的过程，它通过几个阶段发生：肽合成、转运、脂质积累以及通过分泌途径运输。多个控制点调节载脂蛋白的合成和分泌。转录、翻译和细胞内降解的调节代表了独立的调节机制。脂蛋白与脂质共翻译结合的能力似乎对分泌颗粒的形成至关重要。这个过程可能仅由微粒体甘油三酯转移蛋白调节，或者可能被脂质合成酶的活性所改变。大量证据支持甘油三酯和胆固醇酯合成的作用，尽管这两种脂质的相对重要性是主要争议的来源。总之，当所有脂蛋白成分的可用性大幅降低时，它们都可能限制载脂蛋白B和极低密度脂蛋白的合成。体内的限速成分仍未确定。通过了解脂蛋白合成和组装是如何被调节的，应该有可能设计出以有益方式改变这些过程的新方法。
