title: Control of chylomicron export from the intestine.
abstract: The control of chylomicron output by the intestine is a complex process whose outlines have only recently come into focus. In this review we will cover aspects of chylomicron formation and prechylomicron vesicle generation that elucidate potential control points. Substrate (dietary fatty acids and monoacylglycerols) availability is directly related to the output rate of chylomicrons. These substrates must be converted to triacylglycerol before packaging in prechylomicrons by a series of endoplasmic reticulum (ER)-localized acylating enzymes that rapidly convert fatty acids and monoacylglycerols to triacylglycerol. The packaging of the prechylomicron with triacylglycerol is controlled by the microsomal triglyceride transport protein, another potential limiting step. The prechylomicrons, once loaded with triacylglycerol, are ready to be incorporated into the prechylomicron transport vesicle that transports the prechylomicron from the ER to the Golgi. Control of this exit step from the ER, the rate-limiting step in the transcellular movement of the triacylglycerol, is a multistep process involving the activation of PKCζ, the phosphorylation of Sar1b, releasing the liver fatty acid binding protein from a heteroquatromeric complex, which enables it to bind to the ER and organize the prechylomicron transport vesicle budding complex. We propose that control of PKCζ activation is the major physiological regulator of chylomicron output.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee; and Department of Medicine, Veterans Affairs Medical Center, Memphis, Tennessee.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Mansbach
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee; and Department of Medicine, Veterans Affairs Medical Center, Memphis, Tennessee ssiddiq3@uthsc.edu.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Siddiqi
mesh_terms: D000818:Animals; D002914:Chylomicrons / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D021381:Protein Transport; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D002914:Chylomicrons
keywords: PKCzeta; chylomicrons; diacylglycerolacyltransferase; microsomal triglyceride transport protein; monoacylglcerolayltransferase