Lipids Fatty acids, Lipoproteins, Phospholipids, Triglycerides

Oxidation of polyunsaturated fatty acids (PUFA) in lipoproteins may be mediated by reactive species such as radicals, transition metals, other electrophiles, and by enzymes. Once initiated, oxidation of lipids may proceed by a chain reaction, illustrated in Fig. 4 (R5). In step I, an oxidant captures an electron from a PUFA to produce a lipid radical. In step 2, after rearrangement, the conjugated diene radical reacts rapidly with singlet oxygen to produce a lipid peroxide radical, which is the kinetically preferred reaction (step 3) (B5). The chain can be terminated if the lipid radical reacts with an antioxidant to produce a stable peroxide (step 4). Otherwise, the peroxyl radical can react with another polyunsaturated fatty acid as shown in step 5 to perpetuate a chain reaction. The chain reaction requires production of lipid peroxides, giving it the name peroxidation. Fatty acids oxidized in the core are largely triglycerides and cholesterol esters, while toward the outer layer fatty acids in phospholipids are oxidized. 

Fatty acids can be esterifled to glycerol to form diacylglyc-erol, which can enter the phospholipid biosynthetic pathway or, with the addition of a third fatty acid, can be converted into triacylglycerol (TAG, triglyceride). TAGs represent the predominant storage lipid but are also present in blood plasma and, in association with cholesterol, are components of lipoprotein particles. 

Cholesterol and triglycerides, as the major plasma hpids, are essential substrates for cell membrane formation and hormone synthesis and provide a source of free fatty acids. Hyperlipidemia is defined as an elevation of one or more of cholesterol, cholesterol esters, phospholipids, or triglycerides. Lipids, being water immiscible, are not present in free form in the plasma but rather circulate as hpoproteins. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. The density of plasma lipoproteins is determined by their relative content of protein and lipid. Density, composition, size, and electrophoretic mobility divide lipoproteins into four classes (Table 21-1). 

Lipids are poorly soluble in water and special mechanisms are required for their transport from one tissue to another. More than 90% of the plasma fatty acids are present in the form of esters such as triglycerides, phospholipids and cholesteryl esters and these, associated with protein, form the plasma lipoproteins. The small amounts of fatty acids which remain unesterified, the so-called free fatty acids (FFA), are present complexed with albumin. Tissues other than the brain can take up these fatty acids and use them directly as a source of energy or convert them into some form of esterified lipid. 

They can be synthesized by the gut, following the absorption of hydrolyzed dietary lipid. They are combined with small amounts of protein, cholesterol and phospholipid to form chylomicrons. These are removed from the blood, mainly by adipose tissue. An enzyme, lipoprotein lipase is responsible for this hydrolysis of the chylomicron triglycerides. The free fatty acids liberated by these processes are resynthesized into triglycerides by the adipose tissue and stored. 

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