Apoprotein lipoprotein lipase activation

Chylomicrons are triglyceride rich and contain apolipoprotein B-48 and the A types. The latter are synthesized in the intestinal tract cells. Additional apoproteins are transferred to the chylomicrons from HDL in circulation the apoE and apoC types. Their site of synthesis is the liver. The chylomicrons are subject to degradation by lipoprotein lipase in the peripheral tissue, especially adipose tissue. Lipoprotein lipase activity is increased by increased blood insulin levels. This enzyme is extracellular, attached to the capillary endothelial cells, and activated by ApoC-II, which is present in the chylomicrons. Lipoprotein lipase causes the hydrolysis of triglycerides, thus decreasing chylomicron size... 

Function Transport dietary TAG and cholesterol from the intestines to the periphery Forward transport of endogenous TAG and cholesterol from liver to periphery Precursor of LDLs Cholesterol transport 1 Reverse transport of cholesterol from periphery to the liver 2 Stores apoprotein C2 and apoprotein E which it supplies to chylomicrons and VLDLs 3 Scavenges and recycles apolipoproteins released from chylomicrons and VLDL following lipoprotein lipase activity in the capillaries... 

Apoprotein C-II, which activates lipoprotein lipase at the cell surface, permitting uptake of fatty acids from chylomicron triacylglycerol. The triacylglycerols are hydrolysed extracellularly, and the free fatty acids are then taken into the cell and re-esterified to triacylglycerol. In the fed state the major site of lipoprotein lipase activity is adipose tissue, but other tissues can also hydrolyse chylomicron triacylglycerol as required. 

Current available information does not permit definitive conclusions on the nature, specificity, and mechanism of action of the protein cofactor (s) of lipoprotein lipase. It is verj difiicult to correlate the observations described above (summarized in Table 10) since the enzyme preparations used were not pure or well characterized, and were derived from various sources. For instance, two species of lipoprotein lipase have been reported to exist in rat adipose tissue (G4), and major differences between enzymes of liver and adipose tissue have been noted (G16). Also, the nature of the apoprotein preparations employed as protein cofactor (s) of lipoprotein lipase has not been clearly specified in all the studies contaminated materials may account for the spurious results observed. At present, it is not known how apoproteins such as apo Glu, apo Ala, and apo Ser could exhibit their activator or inhibitor activity on lipoprotein lipase. If these different apoproteins indeed prove to be cofactors for lipoprotein lipase, the nature of the lipid-protein specificity must be established and thus the role played by carbohydrates, since some of these apoproteins are glycoproteins. 

Chylomicrons transport dietary triacylglycerol and cholesteryl ester from the intestine to other tissues in the body. Very-low-density lipoprotein functions in a manner similar to the transport of endogenously made lipid from the liver to other tissues. These two types of triacylglycerol-rich particles are initially degraded by the action of lipoprotein lipase, an extracellular enzyme that is most active within the capillaries of adipose tissue, cardiac and skeletal muscle, and the lactating mammary gland. Lipoprotein lipase catalyzes the hydrolysis of triacylglycerols (see fig. 18.3). The enzyme is specifically activated by apoprotein C-II, which... 

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Stocks, J., Galton, D. J. 1980. Activation of the phospholipase Ai activity of lipoprotein lipase by apoprotein C-II. Lipids 15, 186-190. 

A. HDL is produced in the liver. It transfers apoprotein Cn, which activates lipoprotein lipase, to chylomicrons and VLDL. HDL picks up cholesterol from cell membranes. This cholesterol is converted to cholesterol esters by the LCAT reaction. Ultimately, HDL enters liver cells by endocytosis and is digested by lysosomal enzymes. Hormone-sensitive lipase degrades triacylglycerols stored in adipose cells. 

A. The hormone-sensitive lipase of adipose tissue is activated by glucagon via a cAMP-mediated process. Apoprotein CII is the activator of lipoprotein lipase. 

Inhibits VLDL synthesis and apoprotein synthesis in hepatocytes and T HDL —>4- plasma VLDL, LDL, and TGs. Activates lipoprotein lipases. 

Lipoprotein lipase is an enzyme found in the capillaries that catalyzes the hydrolysis of triacylglycerols in chylomicrons to glycerol and fatty acids (Figure 18.6, Figure 18.7). Lipoprotein lipase is activated by apoprotein C-II, which is found in all of the lipoprotein complexes except LDLs. Apoprotein C-1 may also be involved in activation of lipoprotein lipase. 

Fig. 33.24. Conversion of the fatty acid (FA) from the triacylglycerols (TG) of chylomicrons and VLDL to the TG stored in adipose cells. Note that insulin stimulates both the transport of glucose into adipose cells and the secretion of LPL from the cells. Glucose provides the glycerol 3-phosphate for TG synthesis. Insulin also stimulates the synthesis and secretion of lipoprotein lipase (LPL). Apoprotein C-II activates LPL.

Chylomicrons are the largest of the lipoproteins and the least dense because of their rich triacylglycerol content. They are synthesized from dietary lipids (the exogenous lipoprotein pathway) within the epithelial cells of the small intestine and then secreted into the lymphatic vessels draining the gut (see Fig. 32.13). They enter the bloodstream via the left subclavian vein. The major apoproteins of chylomicrons are apoB-48, apoCn, and apoE (see Table 34.3). The apoCn activates lipoprotein lipase... 

Which one of the following apoproteins acts as a cofactor activator of the enzyme lipoprotein lipase (LPL) ... 

The generally held view, for which considerable evidence exists, suggests that lipoprotein lipase exerts its functional activity against chylomicron and VLDL triacylglycerol, following activation by apoprotein-Cji, while both enzyme and substrate are sequestered at the endothelial cell surface of extrahepatic tissue blood vessels. The enzyme and possibly also the substrate are bound to the lumenal surface of the endothelial cells by specific non-covalent interactions with the glycosaminoglycans and proteoglycans present (Cryer, 1981). 

Apolipoproteins undergo changes in secondary protein structure when combined with phosphatidylcholine (Morrisett et al., 1977b). The circular dichroic spectrum and the blue-shifted tryptophan fluorescence spectrum are consistent with an amphipathic structure. Since lipoprotein lipase also can undergo hydrophobic association with phospholipids (Voyta et al., 1980), as indicated by blue-shifted tryptophan fluorescence, it seems probable that the interaction of the enzyme with the apoprotein activator at the lipid-water interface involves extensive lateral protein protein interactions (Smith and Scow, 1979). 

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