Very-low-density lipoprotein assembly and secretion

The assembly of apolipoprotein B (apoB) into VLDL is broadly divided into t wo steps. The first involves transfer of lipid by the microsomal triglyceri de transfer protein (MTP) to apoB during translation. The second involves f usion of apoB-containing precursor particles with triglyceride droplets to form mature VLDL. ApoB and MTP are homologs of the egg yolk storage protein , lipovitellin. Homodimerization surfaces in lipovitellin are reutilized in apoB and MTP to achieve apoB-MTP interactions necessary for first step ass embly. Structural modeling predicts a small lipovitellin-like lipid binding cavity in MTP and a transient lipovitellin-like cavity in apoB important f or nucleation of lipid sequestration. The formation of triglyceride droplet s in the endoplasmic reticulum requires MTP however, their fusion with apoB may be MTP-independent. Second step assembly is modulated by phospholipase D and A2. Phospholipases may prime membrane transport steps required for s econd step fusion and/or channel phospholipids into a pathway for VLDL trig lyceride production. The enzymology of VLDL triglyceride synthesis is still poorly understood; however, it appears that ACAT2 is the sole source of ch olesterol esters for VLDL and chylomicron assembly. VLDL production is cont rolled primarily at the level of presecretory degradation. Recently, it was discovered that the LDL receptor modulates VLDL production through its int eractions with nascent VLDL in the secretory pathway. Curr Opin Lipidol 12: 151-157. (C) 2001 Lippincott Williams & Wilkins.