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2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally Phospholipids They contain glycerol, fatty acids and a nitrogenous base. A.Phosphatidates: i. These are derivatives of phosphatidic acid which is the simplest phospholipid. ii. Phosphatidic acid is made up of one glycerol to which two fatty acid residues are esterified to carbon atoms 1 and 2. The 3rd hydroxyl group is esterified to a phosphoric acid. iii. The molecule has an asymmetric carbon atom and therefore, exhibits optical isomerism. L-isomer is found in nature. B. Amphipathic Nature: Phospholipids in general are amphipathic, particularly Lecithin. They have both hydrophobic and hydrophilic portion in their molecule . The glycerol along with the phosphoric acid and choline constitute the polar ‘head' of a phospholipid molecule, whereas the hydrocarbon chains of the fatty acids represent the nonpolar ‘tail'. 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally C. Micellar Formation When phospholipids are distributed in water, their hydrophobic parts keep away from water, forming molecular aggregates called micelle . These are involved in solubilization of lipids in aqueous media and help in digestion and absorption of lipids. D. Liposomes A lipid bilayer will close on itself under appropriate conditions to form liposomes. Unilamellar or multilamellar liposomes may be formed. They may be prepared by sonication of mixtures of phospholipids and cholesterol . Liposomes are microscopic spherical vesicles. When mixed in water under special conditions, the phospholipids arrange themselves to form a bilayer membrane which encloses some of the water in a phospholipid sphere. Drugs, proteins, enzymes, genes, etc. may be 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally encapsulated by the liposomes which could act as carriers for these substances to target organs. Liposomes have important applications in cancer chemotherapy, antimicrobial therapy, gene therapy, vaccines and diagnostic imaging. E. Biomembranes The molecules align themselves to form monolayers with the polar heads pointing in one direction and the nonpolar tails in the opposite direction . Only fatty acids with more than 6 carbon atoms form monolayers. This explains their role as components of biomembranes The self-assembly of phospholipids into bilayers is driven by hydrophobic interaction. They also act as detergents and emulsifying agents. In vivo, they act as pulmonary surfactants. 1. Phosphatidyl choline or Lecithin i. This is a nitrogen containing phospholipid. The word lecithin is derived from the Greek word, lekithos = egg yolk. It contains glycerol. ii. The alpha and beta positions are esterified with fatty acids. Usually the fatty acid attached to the beta-carbon is a PUFA molecule . iii. The phosphoric acid is added to the third position, to form phosphatidic acid. The phosphate group is esterified to the quaternary nitrogen base, Choline . The molecules of lecithin exist as zwitterions (pl = 6.7). Action of Phospholipases 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally Phospholipases are enzymes that hydrolyse phospholipids. Different phospholipases are involved in the hydrolysis of specific bonds in lecithin . Phospholipase A2 acts on an intact lecithin molecule hydrolysing the fatty acid esterified to the beta (second) carbon atom. The products are Lysolecithin and fatty acid. Lysolecithin is a detergent and hemolytic agent. The enzyme is present in the venom of viper snakes.The hemolysis and consequent renal failure seen in viper poisoning could be thus explained. The products formed in each case may be summarized as follows: Phospholipase A2 Lecithin ——————→ Lysolecithin + fatty acid Phospholipase A1 Lecithin ——————→ Acyl glycerophosphorylcholine+ fatty acid Phospholipase C Lecithin ——————→ 1,2 diacyl glycerol + Phosphoryl choline Phospholipase D Lecithin ——————→ Lung Surfactants Phosphatidic acid +choline 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally Normal lung function depends on a constant supply of lung surfactants. It is produced by epithelial cells. It decreases surface tension of the aqueous layer of lung and prevents collapse of lung alveoli. Constituents of surfactants are dipalmitoyl lecithin, phosphatidyl glycerol, cholesterol and surfactant proteins A, B and C. During fetal life, the lung synthesizes sphingomyelin before 28th week of gestation. But as fetus matures, more lecithin is synthesized. The lecithin-sphingomyelin (LS) ratio of amniotic fluid is an index of fetal maturity. A ratio of 2 indicates full lung maturity. Low levels of surfactant leads to respiratory distress syndrome (RDS), which is a common cause of neonatal morbidity. Respiratory Distress Syndrome (RDS) It is due to a defect in the biosynthesis of dipalmitoyl lecithin (DPL), the main pulmonary surfactant. Premature infants have a higher incidence of RDS because the immature lungs do not synthesize enough DPL. 2. Phosphatidyl ethanolamine or Cephalin Cephalin differs from lecithin in that the nitrogen base ethanolamine is present instead of choline . Cephalin is also found in biomembranes and possesses amphipathic properties. 3. Phosphatidyl inositol 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally Here phosphatidic acid is esterified to inositol . Phosphatidyl inositol bisphosphate or PIP2.is present in biomembranes. This compound plays a vital role in the mediation of hormone action on biomembranes and acts as a second messenger 4. Plasmalogens These are phospholipids which have an aliphatic long chain α − β unsaturated alcohol in ether linkage with the first hydroxyl group of glycerol . The second OH group is esterified to a fatty acid. The phosphoric acid is attached to choline or ethanolamine . The alcohols have about C12 to C18 chain length. Plasmalogens are found in biomembranes in brain and muscle. 5. Phosphatidyl Glycerol 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally It is formed by esterification of phosphatidic acid to glycerol. When two molecules of phosphatidic acid are linked with a molecule of glycerol, diphosphatidyl glycerol or cardiolipin is formed. It is the major lipid of mitochondrial membrane. Commercially, it is extracted from myocardium. Decreased cardiolipin level leads to mitochondrial dysfunction, and is accounted for heart failure, hypothyroidism and some types of myopathies. 6. Sphingolipids The sphingosine containing phosphosphingosides, lipids may glycosphingolipids be and of 3 types; sulfatides. All sphingolipids have the long aliphatic amino alcohol sphingosine which is attached to a fatty acid in amide linkage to form aceramide . The fatty acid has a chain length varying from C18 to C24. 7. Phosphosphingosides They contain phosphoric acid group. A common phosphosphingoside present abundantly in bio membranes, especially of the nervous system, is sphingomyelin. It contains choline . 2016 Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally Sphingomyelins Sphingomyelins are the only sphingolipid that contain phosphate and have no sugar moiety. They are found in large quantities in nervous system. Different sphingomyelins may be formed depending on the fatty acid attached. Common fatty acids found are—lignoceric (24 C), nervonic (24 C, one double bond) and cervonic (22 C, 6 double bonds) acids .Because of its amphipathic nature sphingomyelin can act as an emulsifying agent and detergent. The relative proportion of lecithin and sphingomyelin is important in biological fluids like bile, amniotic fluid, etc. Sphingomyelin combined with fatty acid is called ceramide, which is a component of glycosphingolipids.