The Formation and Intracellular Transport of Chylomicrons

Dietary fat requires hydrolysis within the intestinal lumen prior to absorption. Once absorbed, the fatty acids (FA) and sn-2-monoacylglycerol (MAG) must be rapidly disposed of or the enterocytes risk membrane disruption. This is accomplished by their incorporation into the physico-chemically inert triacylglycerol (TAG). The TAG crosses the ER membrane and is incorporated into the developing chylomicron in a two-step process. In the first step, newly translated apolipoprotein B48 (apoB48) is chaperoned by the microsomal triglyceride transport protein (MTP) in the ER lumen where the apoB48 participates in the formation of the primordial, dense chylomicron consisting of apoB48, phospholipids, cholesterol and a small amount of TAG. This dense chylomicron then combines with a TAG, cholesterol ester rich lipid particle to form the pre-chylomicron within the ER lumen. The pre-chylomicron is then selected for inclusion in the prechylomicron transport vesicle (PCTV) that transports the pre-chylomicron to the cis Golgi. The PCTV budding step is rate limiting for this process. PCTV budding requires liver fatty acid transport protein (L-FABP) or cytosol and ATP. Vesicle associated membrane protein 7 (VAMP7) helps direct the vesicle to its cognate SNARE complex on the cis Golgi. rLFABP generated PCTV do not associate with the Golgi. The fused PCTV deliver the chylomicrons to the Golgi for additional processing prior to their transport in an unknown vesicle to the basolateral membrane for exocytosis and transport into the lymph. In vivo the amount of chylomicrons delivered to the mesenteric lymph for a given amount of dietary TAG can be proportionally regulated by the amount of phosphatidylcholine present in the intestinal lumen. In vitro PCTV generation may be regulated by the action of PKCζ.