Lipoprotein lipases degradation

Nascent VLDLs are produced in the liver, and are composed predominantly of triacylglycerol. They contain a single molecule of apo B-100. Like nascent chylomicrons, VLDLs receive apo C-ll and apo E from HDLs in the plasma. VLDLs carry triacylglycerol from the liver to the peripheral tissues, where lipoprotein lipase degrades the lipid. 

Hoogewerf AJ, Cisar LA, Evans DC, Bensadoun A. Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. J Biol Chem 1991 266 16564-71. 

B. The liver and intestine are the main sonrces of circnlating lipids. Chylomicrons carry triacylglycerides and cholesterol esters from the intestine to other target tissues. VLDLs carry lipids from the liver into circulation. Lipoproteins are a mix of lipids and specific proteins and these complexes are classified based on their lipid/protein ratio. Lipoprotein lipases degrade the triacylglycerides in the chylomicrons and VLDLs with a concurrent release of apoproteins. This is a gradual process which converts the VLDLs into IDLs and then LDLs. 

Lipoproteins in Circulation Are Progressively Degraded by Lipoprotein Lipase... 

The action of lipoprotein lipase lining the blood vessels degrades the triacyl-glycerols, releasing fatty acids locally for cellular uptake. 

These activate lipoprotein lipase which is a key enzyme in degradation of VLDL resulting in lower circulating triglycerides. These drugs lower triglyceride levels by 20-50% with 10-15% decrease in LDL cholesterol and a 10-15% increase in HDL cholesterol. 

Cholesterol and cholesteryl esters are carried in the blood as plasma lipoproteins. VLDL carries cholesterol, cholesteryl esters, and triacylglycerols from the liver to other tissues, where the triacylglycerols are degraded by lipoprotein lipase, converting VLDL to LDL. 

Modification of nascent chylomicron particles The particle released by the intestinal mucosal cell is called a "nascent" chylomicron because it is functionally incomplete. When it reaches the plasma, the particle is rapidly modified, receiving apo E (which is recognized by hepatic receptors) and C apolipoproteins, The latter include apo C-ll, which is necessary for the activation of lipoprotein lipase, the enzyme that degrades the triacylglycerol contained in the chylomicron (see below). The source of these apolipoproteins is circulating HDL (see Figure 18.16). 

Extracellular lipoprotein lipase, activated by apo C-ll, degrades TG in VLDL... 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

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)... 

These lipids are then packaged into spherical lipoproteins, particles of lipids and proteins, known as chylomicrons, which are secreted into lymphatic vessels and subsequently enter the blood stream. Once in the circulatory system the triacylglycerol components of the chylomicrons are degraded to fatty acids and glycerol by the enzyme lipoprotein lipase, which is attached to the luminal (inner) side of capillary vessels in heart, muscle, adipose (commonly... 

The chylomicrons are delivered to other tissues in the body via the bloodstream. In the tissues the chylomicrons bind to the endothelial cells of the capillaries and are degraded to fatty acids and glycerol by lipoprotein lipase. This enzyme is secreted by cells in the tissue and is bound to the endothelial cells. 

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... 

As the lipoproteins are depleted of triacylglycerol, the particles become smaller. Some of the surface molecules (apoproteins, phospholipids) are transferred to HDL. In the rat, remnants that result from chylomicron catabolism are removed by the liver. The uptake of remnant VLDL also occurs, but much of the triacylglycerol is further degraded by lipoprotein lipase to give the intermediate-density lipoprotein (IDL). This particle is converted into LDL via the action of lipoprotein lipase and enriched in cholesteryl ester via transfer from HDL by the cholesteryl ester transfer protein. The half-life for clearance of chylomicrons from plasma of humans is 4-5 min. Patients with the inherited disease, lipoprotein lipase deficiency, clear chylomicrons from the plasma very slowly. When on a normal diet, the blood from these patients looks like tomato soup. A very-low-fat diet greatly relieves this problem. 

The metabolism of cholesterol in mammals is extremely complex. A summary sketch (fig. 20.24) helps to draw the major metabolic interrelationships together. Cholesterol is biosynthesized from acetate largely in the liver (fig. 20.24a) or taken in through the diet (fig. 20.24b). From the intestine, dietary cholesterol is secreted into the plasma mainly as a component of chylomicrons. The triacylglycerol components of chylomicrons are quickly degraded by lipoprotein lipase, and the remnant particles are removed by the liver. Apoproteins and lipid components of the chylomicrons and remnants appear to exchange with HDL. Cholesterol made in the liver (fig. 20.24a) has several alternative fates. It can be (1) secreted into plasma as a component of VLDL,... 

Ostlund-Lindqvist, A.-M., Gustafson, S., Lindqvist, P., Witztum, J. L., and Little, J. A., Uptake and degradation of human chylomicrons by macrophages in culture. Role of lipoprotein lipase. Arteriosclerosis 3, 433-440 (1983). 

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... 

Vitamin E, like neutral lipids, requires apoB lipoproteins at every stage of its transport (Fig. 27-2). Dietary vitamin E becomes emulsified in micelles produced during the digestive phase of lipid absorption and permeates the intestinal epithelium, similar to fatty acids and cholesterol. Uptake of vitamin E by enterocytes appears to be concentration dependent. Within intestinal cells, vitamin E is packaged into chylomicrons and secreted into lymph. During blood circulation of chylomicrons, some vitamin E may be released to the tissues as a consequence of partial lipolysis of these particles by endothelial cell-anchored lipoprotein lipase. The rest remains associated with chylomicron remnants. Remnant particles are mainly endocy-tosed by the liver and degraded, resulting in the release of fat-soluble vitamins. 

The chylomicrons are released into the lymph system and then into the blood. These particles bind to membrane-bound lipoprotein lipases, primarily at adipose tissue and muscle, where the triacylglycerols are once again degraded into free... 

IDL may also be further degraded by lipoprotein lipase, forming LDL. 

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. 

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