Fatty acid metabolism chylomicrons

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

Figure 19.3 Lipoprotein metabolism in the human being. Details of HDL metabolism have been omitted. LPL, lipoprotein lipase FFA, free fatty acids CM, chylomicrons A-E, apoproteins A-E HDL, LDL, IDL, and VLDL are high-density, low-density, intermediate-density, and very low density lipoproteins. (Reproduced by permission from Staff writers. Heart-liver transplantation in a child with homozygous familial hypercholesterolemia. Nutr Rev 43 274-278, 1985.)...

Pancreas Propofol can reportedly cause pancreatitis, perhaps because of alterations in lipid metabolism, leading to hypertriglyceridemia, release of free fatty acids, and chylomicron plugging of pancreatic capillaries. In a retrospective case note review of 479 children with acute leukemia who underwent general anesthesia for a... 

Fig. 3.3. Possible roles of intracellular fatty acid-binding proteins (FABP) in fatty acid metabolism. Fatty acids are delivered to cells by extracellular fatty acid-binding proteins (albumin, lipocalins), by very low-density lipoproteins (VLDL) or by chylomicrons (ChM). After internalization, the FABP may bind the non-esterified fatty acid, and may facilitate their transport to appropriate subcellular sites where metabolism takes place.

The clearance of labeled chylomicrons from the blood is rapid, the half-time of disappearance being under 1 hour in humans. Larger particles are catabolized more quickly than smaller ones. Fatty acids originating from chylomicron triacylglycerol are delivered mainly to adipose tissue, heart, and muscle (80%), while about 20% goes to the liver. However, the liver does not metabolize native chylomicrons or VLDL significantly thus, the fatty acids in the liver must be secondary to their metabolism in extrahepatic tissues. 

The metabolism of VLDL is very similar to that of chylomicrons, the major difference being that VLDL are assembled in hepatocytes to transport triglyceride containing fatty acids newly synthesized from excess glucose, or retrieved from the chylomicron remnants, to adipose tissue and musde. ApoB-100 is added in the hepatocytes to mediate release into the blood. Like chylomicrons, VLDL acquire apoC-II and apoE from HDL in the blood, and are metabolized by lipoprotein lipase in adipose tissue and musde. 

Metabolism of the monoacylglycerol and fatty acids in the enterocyte formation of chylomicrons... 

Lipoprotein metabolism. Entero-cytes release absorbed lipids in the form of triglyceride-rich chylomicrons. Bypassing the liver, these enter the circulation mainly via the lymph and are hydrolyzed by extrahepatic endothelial lipoprotein lipases to liberate fatty acids. The remnant particles move on into liver cells and supply these with cholesterol of dietary origin. 

Apo C-ll activates lipoprotein lipase, which degrades the chylomicron s triacylglycerol to fatty acids and glycerol. The fatty acids that are released are stored (in the adipose) or used for energy (by the muscle). The glycerol is metabolized by the liver. Patients with a deficiency of lipoprotein lipase or apo C-ll show a dramatic accumulation of chylomicrons in the plasma (type 1 hyperlipoproteinemia, familial lipoprotein lipase deficiency, or hypertriacylglycerolemia)... 

Chylomicrons are synthesized in the intestine and transport dietary triacylglycerols to skeletal muscle and adipose tissue, and dietary cholesterol to the liver. At these target tissues the triacylglycerols are hydrolyzed by lipoprotein lipase on the surface of the cells and the released fatty acids are taken up either for metabolism to generate energy or for storage. The resulting cholesterol-rich chylomicron remnants are transported in the blood to the liver where they are taken up by receptor-mediated endocytosis. 

Vitamin E plays an important role in cell metabolism as an antioxidant for the elimination of reactive oxygen intermediates. Subsequent to intestinal resorption, vitamin E is transported in chylomicrons into the liver, from where it reaches other organs together with VLDL. Vitamin E deficiency is observed in chronic liver diseases caused by alcohol, Wilson s disease, haemochromatosis and abetalipoproteinaemia. In vitamin E deficiency, neurologic disturbances (areflexia, dysbasia, ocular palsy, reduced perception of vibration) occur haemolysis can likewise be induced or become more pronounced due to epoxide formation of unsaturated fatty acids within the erythrocyte membranes. 

Figure 6-1. Overview of lipid metabolism in the fed state. TG = triacylglycerol 2-MG = 2-monoacylglyceroi FA = fatty acid LPL = lipoprotein lipase VLDL = very-low-density lipoprotein HDL = high-density lipoprotein circled TG = triacylglycerols of VLDL and chylomicrons.

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