Very-low-density lipoprotein assembly and secretion.
The assembly of apolipoprotein B (apoB) into VLDL is broadly divided into two steps. The first involves transfer of lipid by the microsomal triglyceride transfer protein (MTP) to apoB during translation. The second involves fusion 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 assembly. Structural modeling predicts a small lipovitellin-like lipid binding cavity in MTP and a transient lipovitellin-like cavity in apoB important for nucleation of lipid sequestration. The formation of triglyceride droplets 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 second step fusion and/or channel phospholipids into a pathway for VLDL triglyceride production. The enzymology of VLDL triglyceride synthesis is still poorly understood; however, it appears that ACAT2 is the sole source of cholesterol esters for VLDL and chylomicron assembly. VLDL production is controlled primarily at the level of presecretory degradation. Recently, it was discovered that the LDL receptor modulates VLDL production through its interactions with nascent VLDL in the secretory pathway.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. gshelness@wfubmc.edu
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D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D011973:Receptors, LDL / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism; D014819:Vitellogenins / Q000737:chemistry
D001055:Apolipoproteins B; D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; D014819:Vitellogenins; C106092:microsomal triglyceride transfer protein; D010740:Phospholipases