The Metabolism of Plasma Lipoproteins

The reverse cholesterol pathway is mediated by HDL. HDL is formed from precursor particles originating from the intestine and the liver. In addition, surface 

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Portman, O.W., Alexander, M. 1976. Influence of lysophosphatidyl choline on the metabolism of plasma lipoproteins. Biochim. Biophys. Acta 450, 322-334. 

What is the role of lysosomes in the metabolism of plasma lipoproteins ... 

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

Havel JH, Kane JP. Introduction Structure and metabolism of plasma lipoproteins. In Scriver CR, Blaudet AL, Sly WS, Valle D, editors. The Metabolic Basis of Inherited Disease, eighth ed. New York McGraw-Hill, 2001 2705-2716. 

Unlike most plasma proteins and red blood cells, the metabolism and disposition of plasma lipoproteins is highly regulated and mediated in part by specific receptors located at discreet sites around the body. The concentrations of plasma lipoproteins in the blood can also vary significantly (up to tenfold) as a function of diet, disease, and both within and between healthy individuals. The implications, therefore, for the clearance of drug molecules associated with these plasma lipoproteins are considerable but have not been clearly defined. 

Metabolism of plasma lipoproteins and related genetic diseases. CM=chylomicron, TG=triacylglycerol, VLDL=very low density lipoprotein, LDL=low density lipoprotein, IDL=intermediate density lipoprotein, apo Cll= apolipoprotein Cl I found in chylomicrons and VLDL. The Roman numerals in the white circles refer to specific genetic types of hyperlipidemias summarized on the facing page. 

Though many of these tissue abnormalities remain to be explained, the totality of the abnormalities seen in familial LCAT deficiency provides striking evidence for the importance of the LCAT reaction in plasma lipoprotein metabolism, emd shows how failure to form CE in the plasma can influence the composition and function of tissues. The possibihty that renal glomeruli are particularly sensitive to the composition of plasma lipoproteins clearly deserves to be explored. 

Milk contains substantial amounts of an indigenous lipoprotein lipase (LPL) which is well characterized (Olivecrona and Bengtsson-Olivecrona, 1991 Olivercrona et al, 1992). The physiological role of LPL is in the metabolism of plasma triglycerides and, although it is generally believed that LPL occurs in milk as a result of leakage, it may have a function... 

It is the purpose of this review to cover recent knowledge on chemistry and metabolism of plasma lipoprotein as related to physiological and disease states. Earlier accounts on the subject can be found in the articles by Lindgren and Nichols (1960), Gurd (1960), and Oncley (1963). Most of this discussion will be concerned with lipoproteins of human plasma, which have been studied more extensively than those of other animal species. 

Lamon-Fava, S., Diffenderfer, M.R., Barrett, P.H., Buchsbaum, A., Nyaku, M., Horvath, K.V., Asztalos, B.F., Otokozawa, S., Ai, M., Matthan, N.R., Lichtenstein, A.H., Dolnikowski, G.G., and Schaefer, E.J., 2008. Extended-release niacin alters the metabolism of plasma apolipoprotein (apo) A-I and apoB-containing lipoproteins. Arteriosclerosis, Thrombosis, and Vascular Biology. 28 1672-1678. 

In the long term, failure of glycaemic control and a persistently high plasma glucose concentration results in damage to capillary blood vessels (especially in the retina, leading to a risk of blindness), kidneys and peripheral nerves (leading to loss of sensation) and the development of cataracts in the lens of the eye and abnormal metabolism of plasma lipoproteins (which increases the risks of atherosclerosis and ischaemic heart disease). Two mechanisms have been proposed to explain these effects ... 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

E4. Eisenberg, S., Bilheimer, D. W., and Levy, R. I., The metabolism of very low density lipoproteins proteins. II. Studies on the transfer of apoproteins between plasma lipoproteins. Biochim. Biophys. Acta 280, 94-104 (1972). 

The final two metabolic fates of lipids involve specialized mechanisms for the transport of insoluble lipids in the blood. Fatty acids are converted to the phospholipids and TAGs of plasma lipoproteins, which carry... 

All of these biological roles of the steroids figure prominently in human well-being. Defects in cholesterol metabolism are major causes of cardiovascular disease. It is no wonder that steroids are a central concern in medical biochemistry. In this chapter we discuss the metabolism of these complex lipids and the plasma lipoproteins in which they and other complex lipids are transported to various tissues. 

Unesterified fatty acids are carried in plasma by albumin (chapter 18). The plasma also transports more complex lipids (cholesterol, triacylglycerols) among the various tissues as components of lipoproteins (spherical particles composed of lipids and proteins). Because cholesterol and triacylglyc-erol are insoluble in an aqueous medium such as the plasma, these lipoproteins (which are soluble in plasma) have evolved for the purpose of transporting complex lipids among tissues. In this section we are concerned with the structure and metabolism of these lipoproteins. 

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,... 

In this chapter we dealt primarily with the metabolism of cholesterol, the most prominent member of the steroid family of lipids, and with the associated plasma lipoproteins. The chief points in our discussion are as follows ... 

Relatively little is known about the possible interrelationships of the metabolism of the complex sugar-containing lipids, the glycosphingolipids (GSLs) and the plasma lipoproteins. 

Although hyperlipidemia may be partly reversed by the increase of plasma oncotic pressure with dextran infusion, decreased albumin and plasma oncotic pressure cannot fully explain nephrotic hyperlipidemia. In analbuminemic rats, lipid changes are different from those in nephrotic subjects (D4). There may be a direct causal link between proteinuria and lipid abnormalities because a 1 -acid glycoprotein isolated from urine of nephrotic patients may correct the impaired lipolysis of nephrotic rats (SI 6, K12). Thus, impaired lipoprotein metabolism may be caused by the loss of some regulatory substance into urine due to increased glomerular permeability. 

M15. Mahley, R. W., Innerarity, T. L., Weisgraber, K. H., and Oh, S. Y., Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins. J. Clin. Invest. 64, 743-750 (1979). 

M38. Mjos, O. D., Faergeman, O., Hamilton, R. L., and Havel, R. J., Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat. J. Clin. Invest. 56, 603-615 (1975). 

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