Hdl Takes Part In Both Lipoprotein Triacylglycerol Cholesterol Metabolism

HDL is synthesized and secreted from both liver and intestine (Figure 25-5). However, apo C and apo E are synthesized in the liver and transferred from liver HDL to intestinal HDL when the latter enters the plasma. A major function of HDL is to act as a repository for the apo C and apo E required in the metabolism of chylomicrons and VLDL. Nascent HDL consists of discoid phospholipid bilayers containing apo A and free cholesterol. These lipoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithin:cholesterol acyltransferase (LCAT) and in the plasma of patients with obstructive jaundice. LCAT—and the LCAT activator apo A-I— bind to the disk, and the surface phospholipid and free cholesterol are converted into cholesteryl esters and

Figure 25-4. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL). (A, apolipoprotein A; B-100, apolipoprotein B-100; ©, apolipoprotein C; E, apolipoprotein E; HDL, high-density lipoprotein; TG, triacylglycerol; IDL, intermediate-density lipoprotein; C, cholesterol and cholesteryl ester; P, phospholipid.) Only the predominant lipids are shown. It is possible that some IDL is also metabolized via the LRP.

Figure 25-4. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL). (A, apolipoprotein A; B-100, apolipoprotein B-100; ©, apolipoprotein C; E, apolipoprotein E; HDL, high-density lipoprotein; TG, triacylglycerol; IDL, intermediate-density lipoprotein; C, cholesterol and cholesteryl ester; P, phospholipid.) Only the predominant lipids are shown. It is possible that some IDL is also metabolized via the LRP.

lysolecithin (Chapter 24). The nonpolar cholesteryl esters move into the hydrophobic interior of the bilayer, whereas lysolecithin is transferred to plasma albumin. Thus, a nonpolar core is generated, forming a spherical, pseudomicellar HDL covered by a surface film of polar lipids and apolipoproteins. In this way, the LCAT system is involved in the removal of excess unesterified cholesterol from lipoproteins and tissues. The class B scavenger receptor B1 (SR-B1) has recently been identified as an HDL receptor in the liver and in steroidogenic tissues. HDL binds to the receptor via apo A-I and cholesteryl ester is selectively delivered to the cells, but the particle itself, including apo A-I, is not taken up. The transport of cholesterol from the tissues to the liver is known as reverse cholesterol transport and is mediated by an HDL cycle (Figure 25-5). The smaller HDL3 accepts cholesterol from the tissues via the ATP-binding cassette transporter-1 (ABC-1). ABC-1 is a member of a family of transporter proteins that couple the hydrolysis of ATP to the binding of a substrate, enabling it to be transported across the membrane. After being accepted by HDL3, the cholesterol is then esterified by LCAT, increasing the size of the particles to form the less dense HDL2. The cycle is completed by the re-formation of HDL3, either after selective delivery of cholesteryl ester to the liver via the SR-B1 or by hydrolysis of HDL2 phospholipid and triacylglycerol by hepatic lipase. In addition, free apo A-I is released by these processes and forms preP-HDL after associating with a minimum amount of phospholipid and cholesterol. PreP-HDL is the most potent form of HDL in inducing cholesterol efflux from the tissues to form discoidal HDL. Surplus apo A-I is destroyed in the kidney.

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDL2 concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDLc (HDLj) is found in

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesterol transport. (LCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL, phospholipid; A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDL2, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of prep-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDL2 in women.

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesterol transport. (LCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL, phospholipid; A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDL2, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of prep-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDL2 in women.

the blood of diet-induced hypercholesterolemic animals. It is rich in cholesterol, and its sole apolipoprotein is apo E. It appears that all plasma lipoproteins are interrelated components of one or more metabolic cycles that together are responsible for the complex process of plasma lipid transport.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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