Apolipoprotein in lipoproteins

General Considerations on the Role of Apolipoproteins in Lipoprotein Structure... 

PHYSIOLOGICAL ROLES OF PLASMA APOLIPOPROTEINS IN LIPOPROTEIN 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. 

The expression of all these apo-lipoproteins by the RPE, and its ability to form lipoprotein particles suggest that these newly formed lipoproteins may be involved in the transport of lipophilic molecules, including carotenoids, from the RPE to the neural retina and/or to the choroidal blood supply. Testing the roles of apolipoproteins and lipoprotein particles in carotenoid secretion from the RPE is another subject awaiting experimental investigation. 

Apolipoprotein AIV (apo AIV) is produced in the intestine and is found in chylomicrons, VLDL and HDL. It may modulate enzymes involved in lipoprotein metabolism and may serve as a saturation signal [49]. In a study with 144 participants the apo AIV His360Glu polymorphism showed no significant effect on cholesterol lowering in response to statin therapy [50]. 

Rl. Rader, D. J., Cain, W., Zech, L. A., Usher, D., and Brewer, H. B., Jr., Variation in lipoprotein(a) concentration among individuals with the same apolipoprotein(a) isoforms is determined by the rate of lipoprotein(a) production. J. Clin. Invest. 91, 443-444 (1993). 

Salzer, B., Stavljenic, A., Jurgens, G., Dumic, M., and Radica, A., Polymorphism of apolipoprotein E, lipoprotein(a), and other lipoproteins in children with type I diabetes. Clin. Chem. (Winston-Salem, NC) 39, 1427-1432 (1993). 

Fojo SS, Brewer HB (1992) Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. J Intern Med 231 669-677... 

Kane JP, Havel RJ (2001) Disorders of the biogenesis and secretion of lipoproteins containing the apolipoproteins. In Scriver C, Beaudet A, Sly E, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, pp 2717-2752... 

Apolipoproteins The apolipoproteins associated with lipoprotein particles have a number of diverse functions, such as providing recognition sites for cell-surface receptors, and serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. Some of the apolipoproteins are required as essential structural components of the particles and cannot be removed (in fact, the particles cannot be produced without them), whereas others are transfered freely between lipoproteins. Apolipoproteins are divided by structure and function into five major classes, A through E, with most classes having subclasses, for example, apo A-l and apo C-ll. [Note Functions of all of the apolipoproteins are not yet known.]... 

Saha N, Wang G, Vasisht S, Kamboh MI. Influence of two apo A4 polymorphisms at codons 347 and 360 on nonfasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians. Atherosclerosis. 1997, 131 249-255. 

The apolipoproteins serve at least three important kinds of functions in lipoprotein metabolism. 

Perhaps the clearest demonstration of HDL heterogeneity was that by Suenram et al. (S61). When specific antisera to apolipoproteins A-I, A-II, B, C-III, D, E, and F were set up in double diffusion analyses against HDL, reactions of nonidentity were observed between each possible combination of these antisera. The only exception was a reaction of partial identity between antisera to apoA-I and apoA-II, indicating two types of apoA-contain-ing lipoproteins, a major class containing both proteins and a minor one containing only apoA-I. The other apolipoproteins in HDL therefore appear each to be largely peculiar to their own lipoprotein particles, and the nomenclature LpC, LpD, etc., has been used by Alaupovic and co-workers to describe lipoproteins characterized by a single apolipoprotein class (A5-A7). 

Source Largely from Stein E. Lipids, lipoproteins, and apolipoproteins. In Tietz NW, ed. Textbook of Clinical Chemistry. Philadelphia Saunders, 1986, p. 849. 

Apolipoproteins help maintain the structural integrity and solubility of the lipoprotein complexes, and aid in lipoprotein receptor recognition and regulation of certain enzymes in lipoprotein metabolism. 

Traditionally, human LDLs have been defined as those lipoproteins isolated in the density interval between 1.063 g/ml > LDL > 1.019 g/ml. This density interval may be too broad, however, because a substantial contamination with apolipoproteins other than apoB may be present on those lipoproteins at the two extremes of this density range the contaminating apolipoproteins are principally apoE (present on IDEs and HDLs at the low- and high-density extremes of this density interval, respectively) and apo(a) [present on Lp(a) at the high-density extreme]. This contamination was almost absent in the more tightly defined LDL fraction lying between 1.024 and 1.050 g/ml (Chapman et al., 1988). However, it is possible that loosely associated apolipoproteins are normally bound to LDLs in plasma and are subsequently lost during the multiple flotation steps involved in lipoprotein isolation (Mahley and Holcombe, 1977). 

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.

In humans, apoA-IV is found primarily in the free protein (nonlipoprotein) portion of plasma. Although the reason is not clear, it is possible that the lack of class A motif in the amphipathic helical domains of human apoA-IV causes it to associate poorly with the lipoprotein surface. In rats, however, apoA-IV is seen on HDLs. Examination of individual amphipathic helical domains of rat apoA-IV does show the presence of the class A motif in its structure, thus supporting our hypothesis that the class A motif is essential for binding of apolipoproteins to lipoproteins. 

The function of apoE in lipoprotein metabolism is reviewed in the sixth chapter by Karl Weisgraber. The three-dimensional structure of a 22-kDa fragment of human apoE (34.2 kDa) has been solved by X-ray crystallography the relation of this structure to the role of apoE in lipoprotein metabolism is discussed in detail, together with a critical and extensive examination of the chemistry and biology of this apolipoprotein which plays such a central role in lipoprotein metabolism. Apolipoprotein E has three major isoforms in the human population which affect lipoprotein metabolism differently, resulting in different levels of the plasma lipoproteins. The impact of structure on function and how plasma lipid concentrations are affected by the different apoE isoforms are the themes of this important chapter. 

Kafonek SD, Derby CA, Bachorik PS. Biological variability of lipoproteins and apolipoproteins in... 

Schaefer EJ, Blum CB, Levy RI, Jenkins LL, Alaupovic P, Foster DM, Brewer HB, Jr. Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. N Engl J Med 1978 299 905-10. 

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