Lipoprotein assembly and secretion

Lipoprotein assembly and secretion

Plasma lipoproteins are a family of spherical, macro-molecular complexes of lipid and protein, the principal function of which is to transport endogenous lipids (synthesized in the liver) and exogenous lipids (synthesized in the gut from dietary fats) from these sites of production and absorption to peripheral sites of utilization (e.g., oxidation in muscle, incorporation in membranes, or as precur-sors of biologically active metabolites) and storage (e.g., adipose tissue).

In the small intestine, the newly re-esterified TAGs and CEs associate with specific amphipathic proteins and phospholipids in the enterocyte to form the largest and most TAG-rich lipoproteins, known as chylomicrons. The enterocyte is capable of synthesiz-ing three different apoproteins (apo): apoA-I, apoA-IVs and apoB (B-48). The last apoprotein is expressed in two isoforms, the arbitrarily named apoB-100, which is synthesized in the liver, and a shorter relative of B-100, which is produced by the enterocyte and is approximately 48% of the size of B-100 and thus appropriately named apoB-48. While both apopro-teins are products of the same gene, the mRNA undergoes post-transcriptional editing in the entero-cyte to produce a truncated polypepetide. ApoB-48 is produced in the rough endoplasmic reticulum and transferred to the smooth endoplasmic reticulum, where it combines with a lipid droplet, or nascent chylomicron, and then migrates to the Golgi appara-tus. Here, the apoproteins (A-I, A-IV, and B-48) are glycosylated before the chylomicrons eventually leave the enterocyte by exocytosis through the basement membrane, across the intracellular space between the enterocyte and the lacteal, and are finally discharged into the lymphatic vessels.