There are three main pathways responsible for the generation and transport of lipids within the body. Chylomicron Metabolism Since the intestine is primarily an absorptive organ, it must have the means of exporting newly absorbed lipids. 6. Cholesterol synthesis starts with acetyl-CoA, which is used to synthesize hydroxymethylglutaryl-CoA (HMG-CoA). The pharmaceutical industry has taken advantage of this knowledge to lower people's LDL levels with drugs known as statins. The endogenous lipoprotein pathway begins in the liver with the formation of VLDL. Triglycerides and cholesterol combine to form chylomicrons. The chylomicron remnants contain a smaller core of lipids that is enveloped by excess surface components. The intestine secretes chylomicron particles into the lymphatics. Difficulty of measurement has impeded understanding of their metabolism. Abnormalities in the metabolism of VLDL, IDL, and LDL [apolipoprotein B-100 (apoB-100)-containing lipoproteins] and HDL (apolipoprotein A-containing lipoproteins) are associated with risk of atherosclerosis. After unloading their fats, chylomicrons are smaller and referred to as chylomicron remnants. Chylomicrons enter the circulation and travel to peripheral sites. (2) Chylomicron Metabolism Chylomicrons are metabolized in adipose tissue and muscle. These drugs inhibit HMG-\(\ce{CoA}\) … 1. Figure 4 Chylomicron pathway. The enterocyte re-esterifies fatty acids and monoglycerides to form triglycerides and phospholipids. Abnormalities in chylomicron (apolipoprotein B-48-containing lipoproteins) metabolism are associated with risk of pancreatitis. The Pathways of Lipid Transport. Although the proportion of the apoE-dependent/non-LDLR pathway in the overall metabolism of chylomicron remnants is only (null)/1;6, chylomicron remnants do not accumulate in the plasma of the LDLR-deficient humans and animals fed a normal chow (14, 15, 25). for which apo E is a high-affinity ligand. The enzyme, lipoprotein lipase, located on capillary walls, is activated by apoC-II and hydrolyses triglyceride to glycerol and fatty acids. Exogenous pathway for lipid metabolism: Dietary cholesterol and fatty acids are absorbed. Exogenous cholesterol metabolism pathway Endogenous Pathway. 5. The reactions in this initial stage are the same as in ketogenesis (see slide 10.4.1).However, while ketogenesis occurs in the mitochondria, HMG-CoA destined for … Chylomicrons are the ‘orphans’ of the lipoprotein family. Very-low-density lipoproteins (VLDL) contain apoprotein B-100 (apo B), are synthesized in the liver, and transport TGs and cholesterol to peripheral tissues. The triglycerides carried in VLDL are metabolized in muscle and adipose tissue by lipoprotein lipase releasing free fatty acids and IDL are formed. Triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterified. Rate-limiting enzymes limit the rate at which a metabolic pathway proceeds. Plasma concentrations of chylomicrons and chylomicron remnants give no insight into the magnitude of substrate flux through these pathways. The endogenous pathway of lipid metabolism begins with Empty HDL is produced as a byproduct of steps 3 and 4. These surface constituents are transferred from the chylomicron remnant for the formation of high density lipoprotein. Chylomicron remnants are then taken up by the liver. Chylomicron remnants then travel to the liver and are removed by the binding of apoE to their remnant receptor. Peripheral sites their fats, chylomicrons are the ‘ orphans ’ of the lipoprotein family of chylomicrons chylomicron. 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