Plasma lipoproteins, metabolism

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. 

Volume 129. Plasma Lipoproteins (Part B Characterization, Cell Biology, and Metabolism)... 

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. 

Trautwein, E. A., Siddiqui, A., and Hayes, K. C. (1993). Modeling plasma lipoprotein-bile lipid relationships Differential impact of psyllium and cholestyramine in hamsters fed a lithogenic diet. Metabolism 42,1531-1540. 

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). 

PO025 Me Call, M. R., T. Mehta, C. W. Leathers, and D. M. Foster. Psyllium husk I. Effect on plasma lipoprotein, cholesterol metabolism, and artherosclerosis in African green monkeys. Amer J Clin Nutr 1992 56(2) 376-384. 

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... 

Metabolism of chylomicrons. CM = chylomicron TG = triacylglycerol C = cholesterol CE = cholesteryl esters. Apo B-48, apo C-ll, and apo E are apolipoproteins found as specific components of plasma lipoproteins. 

Until 1993 apolipoprotein E was best known for its central role in plasma lipoproteins and cholesterol transport (Fig. 21-1). However, one of the three common alleles of the apoE gene confers a significant risk of development of Alzheimer disease.12171218 A high blood cholesterol level is also correlated with increased risk.12191220 Membrane abnormalities in mitochondria have been associated with Alzheimer disease.1221 Also related to membranes and lipid metabolism, vitamin E appears to combat Alzheimer disease.843 1218... 

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. 

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. 

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. 

PLASMA LIPOPROTEINS, APOLIPOPROTEINS, AND PROTEINS CONCERNED WITH LIPID METABOLISM... 

In this article we shall review recent advances in plasma lipoproteins, apolipoproteins, and those proteins concerned with lipoprotein lipid metabolism. This is a rapidly growing field, far too large to enable all aspects to be covered in a single paper. In order to keep to a manageable size, we shall focus on areas in which there have been recent major advances. Our treatment of other areas will be brief, as adequate reviews are in most cases available. Clinical details of primary disorders of plasma lipid metabolism are very well covered in a series of reviews in The Metabolic Basis of Inherited Disease (5th Ed., J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, eds.) (B52, G13, G20, H24, N8, S3, S56). Disordered lipid metabolism, and especially secondary disorders of lipid metabolism, are equally well covered in Metabolic Control and Disease (8th Ed., P. K. Bondy and L. E. Rosenberg, eds.) (H16). 

The major interest in plasma lipoprotein metabolism for the clinical chemist arises because of the relationship with human disease, especially coronary heart disease. In this respect it is worth noting some of the major recent advances in clinical studies and epidemiology before returning to discuss plasma lipoprotein metabolism. 

Taken together, these studies indicate that lowering plasma cholesterol lowers coronary heart disease risk. The importance of research on normal and abnormal plasma lipoprotein metabolism is emphasized, and is, in part, the justification for this review,... 

It should also be remembered that plasma lipoproteins are constantly in a state of metabolic flux. Some large particles are converted to smaller particles, and vice versa. Lipids and most apolipoproteins exchange or are transferred between particles and particles are released into and removed from the circulation. 

A disorder of lipid metabolism, in which absence of lipoprotein lipase activity due to an absolute apoC-II deficiency results in marked hypertriglyceridemia (Type I phenotype), has been reviewed elsewhere (N8). There are some unexplained differences in the clinical picture and plasma lipoprotein pattern between apoC-II deficiency and primary lipoprotein lipase deficiency. In apoC-II deficiency, symptoms appear to be milder (but recurrent abdominal pain, caused apparently by acute pancreatitis, is a frequently reported symptom). Patients do not show xanthomas or hepatomegaly, and few have splenomegaly (all features of lipoprotein lipase deficiency). Diagnosis is by electrophoresis of the C apolipoproteins, and a plasma triglyceride concentration usually 1000-3000 mg/dl (N8). There may be an increase in plasma VLDL concentration, whereas in classical lipoprotein lipase deficiency plasma VLDL concentration is nearly normal (N8). 

The scale and pace of research on plasma lipoprotein metabolism is such that any review must perforce be incomplete and out of date at the time of publication. In this review we have focused on recent advances, and in particular on those aspects of recent advances which are likely to impinge on clinical chemistry. 

F6. Falko, J. M., Schonfeld, G., Witztum, J. L., Kolar, ]. B., and Salmon, P., Effects of short-term high carbohydrate, fat-free diet on plasma levels of Apo C-II and Apo C-III and on the ApoC subspecies in human plasma lipoproteins. Metabolism 29, 654-661 (1980). 

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). 

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