Apolipoproteins composition

Plasma HDL constitute a heterogeneous group of lipoproteins their common property is that they have a hydrated density in the 1.063-1.21 g/ml interval. HDL subfractions are usually described in terms of their hydrated density, but it should not be forgotten that a number of functions may be the property of particular subsets of HDL which can be defined better in terms of their apolipoprotein composition than their hydrated density. A preparation of HDL isolated by flotation in the ultracentrifuge, d between 1.063 and 1.21 g/ml, may contain almost all the major apolipoproteins (except perhaps apoA-IV and apoB-48), together with LCAT and lipid transfer protein. 

L2. Lagocki, P. A., and Scanu, A. M., In vitro modulation of the apolipoprotein composition of high density lipoprotein. Displacement of apolipoprotein A-I from high density lipoprotein by apolipoprotein A-II. /. Biol. Chem. 255, 3701-3706 (1980). 

Fig. 1. General oil-droplet model of lipoproteins is presented for chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) structures. Apolipoproteins in the outer phospholipid membrane, designated by letters, are defined in Table II. The major differences between the lipoproteins are the size of the neutral lipid (triglyceride and esterified cholesterol) core, liquid composition in the core, and apolipoprotein composition. (E) Triglycerides, ( Q ) phospholipids, and ( -) esterified cholesterol are shown. Although not shown, unesterified cholesterol is found predominantly in the phospholipid monolayer.

Among the problems involved in constructing a general model for vertebrate lipoprotein structure, some of the more important are the heterogeneity in size and apolipoprotein composition and the small number of examples of lipoproteins containing similar apolipoprotein composition, which can be used to validate the model. Thus, in most cases, data as elementary as the stoichiometry of the apolipoproteins cannot be included in the models (Shen et ai, 1977) or, if stoichiometry data are included, only a partial fit of the data to the model is observed (Edelstein etal., 1979). 

One of the most intriguing features of lipophorin composition is the large variation in lipid content and composition that can be accommodated without modifications in the apolipoprotein composition of the particles (Table I). This feature makes lipophorin a good system in which to analyze the structure of lipoproteins and the physicochemical factors that govern their structure and properties. In addition to the previously discussed data on the size and shape of lipophorins, several studies on other aspects of lipophorin structure have been performed and need to be discussed before describing models for lipophorin structure. 

Figure 26-18 Exogenous lipoprotein metabolism pathway. TG, Triglyceride CE, cholesterol ester FC, free cholesterol Ft, phospholipids HDL, hIgh-density lipoproteins FA, fatty acid LPL, lipoprotein lipase 6, apolipoprotein B-48 A, apolipoprotein A-i C, apolipoprotein C-ll , apolipoprotein E. (From Rifai N. Lipoproteins and apolipoproteins Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 10 694-701. Copyright 1986, American Medical Association.)...

Rifai N. Lipoproteins and apolipoproteins. Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 110 ... 

Results of these studies are providing additional evidence that distinct lipoprotein families or particles defined by their apolipoprotein composition represent the fundamental chemical and metabolic entities of the lipid transport system. The concept of lipoprotein families thus offers a new theoretical basis for describing, interpreting, and influencing processes responsible for normal as well as defective transport of triglycerides and other lipids. 

Major Apo B-containing lipoprotein families have specific lipid and apolipopro-tein composition. They constitute poly disperse macromolecular systems, heterogeneous with respect to hydrated density, size, and lipid/protein weight ratios, but homogeneous with respect to the qualitative apolipoprotein composition. 

The metabolism of Apo B- and Apo A-containing Upoprotein particles depends on and seems to be affected primarily by their corresponding apolipoprotein composition. 

Among chromatography variants which employ affinity as separating criterion, I would like to mention chromatography over hydoxylapatite. Kostner described this method first and reported eight HDL subfractions which clearly differed in terms of apolipoprotein composition, triglyceride and lipid/protein ratio [6]. The separation principle is not quite clear it is probable that polar interactions with apolipoproteins and the polarity of surface lipids play a role. 

As mentioned above, the large pore size of agarose also allows the subfractionation of VLDL. Upon isoelectric focusing of VLDL which had been isolated by ultracentrifugation, we found three groups of bands which differ in respect to density, Upid and apolipoprotein composition. Functional differences were seen after an oral fat load and upon heparin-induced lipolysis. Acidic subfractions rich in triglycerides and apolipoprotein C-III increased after the fat load and were apparently the preferred substrate for the action of heparin-released lipases (Fig. 3). 

In conclusion, there are a number of techniques which allow the subfractionation of Upoproteins. However, we know that apolipoproteins are constituents which strongly determine the metabolic fate of most lipoprotein particles. Therefore, methods which subfractionate lipoproteins according to apolipoprotein composition deserve the preferred attention of any researcher who investigates functional aspects of lipoprotein subfractions. 

Recently, in cooperation with Eugene Koren and Pierre Alaupovic, we have developed new methodologies for what we call the molecular analysis of lipoprotein particles. This report briefly presents an inununoenzymometric assay which allows the separation of particles according to their apolipoprotein composition or according to epitope expression of one apolipoprotein on their surface. 

The results presented here substantiate the usefulness of the study of lipoprotein particles defined by their apolipoprotein composition for future clinical, pharmacological, and epidemiological studies. This approach might also improve our understanding of lipoprotein metabolism and different physiopathological states. 

The lipoproteins present in plasma may be operationally defined according to their density, as low or very low density lipoproteins and high density lipoproteins, but other, more functional definitions may be more appropriate in connection with in vivo metabolism. Examples are the hpoprotein classes chylomicrons and chylomicron remnants. Alaupovic has suggested a classification based on the apolipoprotein composition [1]. As apolipoproteins often determine the metabolic fate of lipoprotein particles this is a logical approach. Lipoprotein particles with specific apolipoprotein compositions exist in all density fractions of human plasma, as well as plasma from a variety of animal species. 

It is clear that the distributions may differ substantially between hypertrigly-ceridemic and hypercholesterolemic states. How may these apolipoprotein compositions influence metabolism In order to answer this type of basic question it is often necessary to turn to animal experiments. 

Wang C-S, Alaupovic P, Gregg RE, Brewer HB Jr (1987) Studies on the mechanism of hypertriglyceridemia in Tangier disease. Determination of plasma hpolytic activities, Kj values and apolipoprotein composition of the major lipoprotein density classes. Biochem Biophys Acta 920 9-19... 

As we pointed out in section 5.3.5(a), lipoproteins are not discrete particles of fixed size but form a distribution of sizes thus the sizes and densities of IDL or remnant particles overlap those of the precursor VLDL or the product LDL but can be distinguished by their mobility on electrophoresis, presumably because of their different apolipoprotein composition. 

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