High density lipoproteins protein moiety

Cholesteryl esters that are internalized via the LDL receptor are hydrolyzed to produce cholesterol and an acyl chain. Cholesterol, in (urn, activates the enzyme acyl-CoA cholesterol acyl-transferase (ACAT) which re-esterifies cholesterol. In an apparently futile cycle, the cholesteryl esters are hydrolyzed by cholesteryl ester hydrolase. The cholesterol moiety has several fates it may leave the cell and bind to an acceptor such as high-density lipoprotein (HDL), it may be converted to steroid hormones, or it may be reesterified by ACAT. When the cellular cholesterol concentration falls, the activity of HMG-CoA reductase is increased, as is the number of LDL receptors, which results in an increase of cellular cholesterol, due both to de novo synthesis and to the uptake of cholesterol-rich lipoproteins in the circulation. An increase in cellular cholesterol results in the rapid decline in the mRNA levels for both HMG-CoA reductase and the LDL receptor. This coordinated regulation is brought about by the presence of an eight nucleotide sequence on the genes which code for both proteins this is termed the sterol regulatory element-1. 

The protein moiety of newly synthesized TG-rich lipoproteins consists only of apo B. After secretion, other apolipoproteins are exchanged on to the particles from high-density lipoprotein (HDL) particles in the circulation. As TG is hydrolyzed by endothelial lipases (ELs) (Section 2), these extra proteins are displaced from the particle surface. 

A contribution to the understanding of lipoprotein metabolism would be the definition of the metabolic role of the lysolecithin-rich d 1.21 lipoprotein. This protein-phospholipid complex may simply represent a degradation product of the high-density lipoprotein after removal of the other lipid moieties. On the other hand, it could be considered as a newly synthesized product from the liver on its way to further lipidation to form a more complete class of lipoproteins. Its possible identity with the apolipoprotein described by Roheim and Eder (1961 Roheim et al., 1964) remains to be established. 

Attempts have been made in the author s laboratory to obtain a lipid-free water-soluble product from the d < 1.019 and d 1.019-1.063 low-density human serum lipoproteins by using the ethanol-ether procedure successfully applied to the high-density class (Scanu et al., 1958a). The precipitate obtained proved insoluble in the various buffered media alone or in the presence of 1-4 M urea. Banaszak and McDonald (1962) attempted separation of the protein moiety of d 1.019-1.063 serum lipoproteins by a pentane extraction of a lyophilized preparation. The product obtained, insoluble in common buffer solutions, was solubilized in carbonate buffer of pH 10.2 in the presence of 4 M urea, leading to prompt formation of a gel, which persisted after removal of urea by dialysis. 

After entry in the blood stream the chylomicrons are hydrolyzed by the endothelial-bound lipoprotein lipase with apo C-I as a co-factor, allowing the delivery of free FAs to muscle and adipose tissue. The chylomicron remnants are rapidly taken up into the liver via especial receptor. ApoE is the moiety required for rapid hepatic removal. Its activity is inhibited by C apolipoproteins, especially apoC-I. The liver utilizes the exogenous fat and can release surplus lipids via VLDL into the blood. The VLDL is another substrate for lipoprotein lipase. The remaining VLDL remnants can either be taken up into the liver or are hydrolyzed to LDL. These last delivers cholesterol to all body cells via its receptor [136]. Moreover other type of lipoprotein denominated as high-density protein (HDL) is an important scavenger of surplus cholesterol transporting it from cell membranes to the liver, where it is degraded or converted into biliary salts, an then eliminated by the entero-hepatic cycle [137]. 

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