**1. Introduction**

646 Lipoproteins – Role in Health and Diseases

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Lipoproteins are complex aggregates of lipids and proteins that render endogenous lipids compatible with the aqueous environment of body fluids (Brown, 2007). The major physiological role of lipoproteins is to transport water-insoluble lipids from their point of origin to their respective destinations. Lipoproteins are synthesised mainly in the liver and intestines. They are in a state of constant flux, in circulation, changing in composition and physical structure as the peripheral tissues take up the various components before the remnants are returned to the liver. The most abundant lipid constituents of lipoproteins are free cholesterol, cholesterol esters, triacylglycerols and phospholipids, though fat-soluble vitamins and anti-oxidants are also found in lipoproteins (Kwiterovich, 2000).

#### **Classification of lipoproteins**

Lipoproteins are classified as chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), based on the relative densities of the aggregates on ultracentrifugation. These classes are further refined by improved separation procedures, and intermediate-density lipoproteins (IDL) and subdivisions of the HDL (e.g. HDL1, HDL2, HDL3 etc) are often defined. Density of lipoproteins is determined largely by the relative concentrations of triacylglycerols and proteins and by the diameters of the broadly spherical particles, which vary from about 6000Å in CM to 100Å or less in the smallest HDL. An alternative nomenclature is based on the relative mobilities on electrophoresis on agarose gels. Thus, α, pre-β and β lipoproteins correspond to HDL, VLDL and LDL, respectively (Lacko *et al*., 2007).

#### **Chylomicrons**

Chylomicrons, the largest and least dense of the lipoproteins are formed in the intestinal cell walls from dietary fat and cholesterol. Their main task is to carry triglycerides from the

© 2012 Saba and Ajibade, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

intestine to the tissues where they are needed as a source of energy. In the circulation, triglycerides are removed from chylomicrons via the action of lipoprotein lipase (LPL), an enzyme present in the capillaries of many tissues. If present in large amounts, such as after a fatty meal, chylomicrons cause the plasma to appear milky.

#### **Very low density lipoproteins**

Very low density lipoproteins (VLDLs) are synthesised in the liver. Much like chylomicrons, they function primarily to distribute triglycerides to target sites such as adipose tissue and skeletal muscle where they are used for storage and energy. The manner in which triglycerides are removed from the circulation is the same as that of chylomicrons. Gradually with removal of triglycerides and protein, VLDLs are converted to LDL. High plasma levels of VLDL are associated with familial hypertriglyceridaemia, diabetes mellitus and underactive thyroid.

#### **Low density lipoproteins**

Low density lipoproteins are cholesterol-rich particles. About 70% of plasma cholesterol occurs in this form. LDLs are chiefly involved in the transport of the cholesterol manufactured in the liver to the tissues, where it is used. Uptake of cholesterol into cells occurs when lipoprotein binds to LDL receptors on the cell surface. LDL is then taken into the cell and broken down into free cholesterol and amino acids. Disorders involving a defect in or lack of LDL receptors are usually characterised by high plasma cholesterol levels. The cholesterol cannot be cleared efficiently from the blood and therefore accumulates.

#### **High density lipoproteins**

The high-density lipoproteins (HDLs) are small, dense, and spherical lipid-protein complexes which are normally considered to consist of those plasma lipoprotein particles which fall into the density range of 1.063–1.210 g/mL. HDL particles are composed of an outer layer containing free cholesterol, phospholipid, and various apolipoproteins (Apo), which covers a hydrophobic core consisting primarily of triglycerides and cholesterol esters (Barter *et al*., 2003). The major proteins are Apo A-I (Mr 28,000) and Apo A-II (Mr 17,000). Apo A-I, the primary protein constituent of these particles, accounts for about 60% of the protein content of HDL. Apo A-I is synthesized in the intestines and liver and is thought to be largely responsible for the antiatherogenic effects of HDL. Some HDL particles carry only Apo A-I, whereas others contain both Apo A-I and Apo A-II (Shah *et al*., 2001). Other apolipoprotein species found in HDL particles include Apo A-IV, Apo C (C-I, C-II, and C-III), and Apo E.

#### **High density lipoprotein subtypes**

Several subtypes of HDL particles have been identified on the basis of density, electrophoretic mobility, particle size, and apolipoprotein composition (Albers *et al*., 1984). Differences in particle size are mainly the result of the number of apolipoprotein particles and the volume of the cholesterol ester in the core of the particle. HDL can also be classified into larger, less dense HDL2 or smaller, denser HDL3 which falls within the density ranges 1.063–1.125 and 1.125–1.210 g/mL, respectively. Although the major proportion of HDL is normally present in HDL3, individual variability in HDL levels in human populations usually reflects different amounts of HDL2 (Skinner, 1994). HDL2 is richer in particles containing Apo A-I without Apo A-II, whereas HDL3 is richer in particles containing both Apo A-I and Apo A-II (Gotto, 2001).

#### **Synthesis, Metabolism and Regulation of plasma lipoprotein concentration**

Normal metabolism and homeostasis of carbohydrates, amino acids and lipids *in vivo*  depend on integrated liver function. Most plasma apolipoproteins and endogenous lipids and lipoproteins, including apolipoprotein(a) (apo(a)) and lipoprotein(a) (Lp(a)), are synthesized in the liver. The apolipoprotein(a) is a high molecular weight glycoprotein, of 250-838 kD (Bowden, 1994) and a total of 34 different apo(a) isoforms have been identified in populations (Marcovina *et al*., 1993). The core components of Lp(a) are neutral lipid and an apoB-100 molecule, which are covalently connected by a disulfide-bond bridge and surrounded by hydrophilic apo(a) (Byrne, 1994). The heterogeneity of apo(a) determines the changes in plasma Lp(a) concentrations, and there is a negative correlation between the molecular weight of apo(a) and the plasma Lp(a) concentration (Wade, 1993)

Lp(a) has a simple Mendelian dominant inheritance, which is controlled by the alleles Lpa and Lp0 (Utermann *et al*., 1988). Plasma Lp(a) concentration is controlled by three alleles., i.e., LpA, Lpa and Lp0 (Hasstedt *et al*. 1986). Pedigree analysis indicated that the size polymorphism of Lp(a) is controlled by a series of alleles of a single point (Utermann, 1988). The apo(a) gene which is located in q26-27 of chromosome 6 in humans has a linkage to the plasminogen (PGN) gene, and is inherited in a codominant Mendelian model (Amemiya, 1996). Apolipoprotein(a) mRNA (14 kb) encodes for a mature protein of 4529 amino acid residues in the presence of a signal peptide with 19 amino acid residues (McLean, 1987) while a high-degree homology exists between the molecular structures of the apo(a) gene and the PGN gene. The high-degree homology between the apo(a) gene and the PGN gene determines the biological actions of Lp(a) (Romics *et al*., 1996).
