| MTP (microsomal triglyceride transfer protein) heterodimerizes with protein disulfide isomerase to form the lipid transfer machinery essential for apolipoprotein B-containing lipoprotein assembly in hepatocytes and enterocytes. MTP organizes lipid-binding pockets within a boomerang-shaped scaffold that accommodates neutral lipids like triglycerides and cholesteryl esters alongside promiscuous sites for phospholipids and sphingolipids, enabling bulk transfer between donor and acceptor membranes through transient hydrophobic channel formation. MTP physically associates with newly translated apoB via its N-terminal 100 residues, catalyzing sequential lipidation steps where initial phospholipid transfer stabilizes apoB folding followed by triglyceride loading that expands a primordial lipid pocket into a voluminous core priming pre-VLDL/chylomicron particles for Golgi maturation and secretion. Insulin suppresses MTP promoter activity through FoxO1 phosphorylation and nuclear exclusion alongside SREBP-1c mediated competition at sterol regulatory elements, while LXR agonists enhance expression via DR4 motifs coordinating hepatic VLDL output to dietary fat availability. Cholesterol loading allosterically inhibits MTP activity through direct binding that occludes the transfer tunnel, coupling sterol sensing to lipoprotein production rates and preventing cellular lipid toxicity during fasting-fed transitions. MTP governs intestinal chylomicron emulsification of dietary triglycerides alongside hepatic VLDL export, sustaining systemic fatty acid delivery to peripheral tissues, with peak expression in absorptive enterocytes and periportal hepatocytes reflecting postprandial demands. Complete MTP deficiency manifests as abetalipoproteinemia with fat malabsorption, acanthocytosis, and spinocerebellar degeneration from vitamin E deficiency, while partial dysfunction associates with NAFLD through impaired VLDL-mediated triglyceride clearance. |
Lane 1: Mouse liver, Lane 2: Rat liver
