L25 Complex Lipids.pdf

L25 Complex Lipids: Structure and Functions Dr. Nelofar Khan www.gmu.ac.ae COLLEGE OF MEDICINE Learning objectives The student should be able to: 1. Define complex lipids and give examples. 2. List various phospholipids and glycolipids and mention their functions. 3. Define sphingolipidoses....

L25 Complex Lipids: Structure and Functions Dr. Nelofar Khan www.gmu.ac.ae COLLEGE OF MEDICINE Learning objectives The student should be able to: 1. Define complex lipids and give examples. 2. List various phospholipids and glycolipids and mention their functions. 3. Define sphingolipidoses. References: • Reading: Satyanarayana U and Chakrapani U. Biochemistry; Elsevier; 5th Edition; 2020. ISBN- 978-8131262535. Chapter 3, pages 34 - 37. COMPOUND OR COMPLEX LIPIDS Fatty Acid + Alcohol + Some other groups It includes: I. Phospholipids II. Glycolipids III. Sulpholipids ▪ All these are amphipathic as they contain both hydrophobic and hydrophilic regions in the same molecule. ▪ They are important structural and functional components of the biomembranes. ▪ Act as detergents and emulsifying agents in the bile. ▪ Components of lung surfactants. I. PHOSPHOLIPIDS Fatty Acid + Phosphoric Acid + Nitrogen base [other compound] • Phospholipids are grouped depending upon the alcohol present into : a) GLYCEROPHOSPHOLIPID (containing glycerol) It includes 1) Phosphatidic acid 2) Lecithin 3) Cephalin 4) Cardiolipin 5) Phosphatidyl Inositol b) SPHINGOPHOSPHOLIPID (containing sphingosine) Typical Phospholipid Lipid Bilayer GLYCEROPHOSPHOLIPIDS PHOSPHATIDIC ACID: • It is the simplest phospholipid. • It usually does not occur free in nature but is an intermediate in the synthesis of other phospholipids and TAG’s. Glycerol + 2 FA’s + PO4 Enzymes hydrolyzing phospholipids • PHOSPHOLIPASE- A1 Attacks the bond at position 1 of glycerol and FA. Present in many mammalian tissues. • PHOSPHOLIPASE A2 Attacks the bond at position 2. Present in many mammalian tissues & pancreatic juice (as proenzyme). Also present in snake and bee venoms. • PHOSPHOLIPASE-B Hydrolysis both acyl groups. LYSOPHOSPHOLIPIDS It is a result of the action of phospholipases A1 or A2. PL - FA = LysoPL Lysolecithin is a detergent and hemolytic agent. LECITHIN (Phosphatidyl Choline) • Fatty acid attached to the β-carbon is a PUFA molecule. • These are the most abundant group of phospholipids in the cell membrane. Fatty Acid + Glycerol + Phosphoric acid + Choline Dipalmitoyllecithin (Lung surfactant) Palmitic acid present at both C-1 &C-2 positions of glycerol. Present in large amounts in the extracellular liquid layer that lines the alveoli of normal lungs. It decreases the surface tension of the aqueous surface layer of the lungs and prevents atelactasis at the end of the expiration phase of breathing. Its absence from the lungs of premature infants causes respiratory distress syndrome RDS. Lysolecithin Phospholipase A2 acts on intact lecithin molecule hydrolyzing the FA esterified to the β-carbon atom result in formation of Lysolecithin. Lecithin Phospholipase A2 Lysolecithin + FA Lysolecithin is a detergent and hemolytic agent. Phospholipase A2 is present in snake venom also. Hemolysis and consequent renal failure seen in viper poisoning is due to the action of phospholipase A2. Phosphatidyl Ethanolamine Phosphatidyl Serine They are present in the lipid bilayer of the membrane. Diphosphatidylglycerol (cardiolipins) • They are found primarily in the inner mitochondrial membrane. • It is also a component of pulmonary surfactant. • Antiphospholipid syndrome (APS) is characterized by recurrent venous or arterial thrombosis (clots), recurrent fetal loss, and thrombocytopenia. • Presence of anticardiolipin antibodies are responsible for APS. PHOSPHATIDYLINOSITOL ▪ Exist in membranes as polyphosphoinositides. ▪ Phosphatidylinositol 4,5-bisphosphate, (PIP2) is involved in the transmission of signals from outside the cell to inside. ▪ Act as second messengers. ▪ Also anchors various proteins to the plasma membrane. • Example: • Serotonin binds to cell surface receptors and triggers the activation of Phospholipase C. It breaks PIP2 into DAG & IP3. DAG + Activate protein Kinase C Phosphorylates other proteins IP3 Release Ca from ER Smooth muscle contraction Most actions of DAG & IP3 are synergistic. Plasmalogens At C-1 (sn1) of glycerol, a long chain unsaturated alcohol is present making an ether linkage. Found in high amounts in biomembranes in brain and muscles. SPHINGOLIPIDS • Composed of a polar head group and two nonpolar tails. • Include sphingomyelins, glycosphingolipids and sulpholipids. • Component of all membranes but are particularly abundant in the myelin sheath of the nervous system. SPHINGOSINE Long-chain amino alcohol, present in all CERAMIDES sphingolipids. Sphingosine N-acetylated by a fatty acids. SPHINGOMYELINS • Ceramide + Phosphorylcholine. • Sphingomyelins are the only sphingolipid that contain phosphate and have no sugar moiety. • Important structural components of nerve cell membranes (myelin sheath). • L/S ratio is important in biological fluids like bile, amniotic fluid. GLYCOSPHINGOLIPIDS (GLYCOLIPIDS) Composed of a ceramide + carbohydrate groups attached to carbon 1 of sphingosine. The four principal classes of glycosphingolipids are: • Cerebrosides • Globosides • Gangliosides • Sulfatides. Cerebrosides: A single sugar group linked to ceramide. The most common is Galactocerebrosides, found predominantly in neuronal cell membranes. Globosides: Ceramide + Oligosaccharide. Lactosyl ceramide is a globoside found in erythrocyte plasma membranes. Gangliosides: Are similar to globosides except that they contain one or more molecules of Sialic Acid (NANA) also. Cholera toxin binds to ganglioside on intestinal mucosal cell – irreversible activation of G protein. Sulpholipids: Sulphate group attached to cerebrosides, globosides, gangliosides. • All these complex lipids are important components of the membranes of nervous tissues. • Failure of degradation of these compounds results in their accumulation in CNS. • This group of inborn errors is known as sphingolipidosis (LIPID STORAGE DISEASES). Micelles and Liposomes Micelles are closed lipid monolayers with a fatty acid core and polar surface. Hydrophillic "head" facing the outside, while the hydrophobic "tails" surround the fat-soluble nutrient inside. Bile salts are involved in micelle formation in intestine, known as emulsification. Liposomes are composed of a lipid bilayer separating an aqueous internal compartment from the bulk aqueous phase. They have important application in drug delivery. Basic Concepts PHOSPHOLIPIDS include: a) Glycerophospholipid (containing glycerol) They are: Phosphatidic acid, Lecithin, Cephalin, Cardiolipin, Phosphatidyl Inositol b) Sphingophospholipid: (Sphingomyelin) SPHINGOLIPIDS (containing sphingosine) Glycosphingolipids: Presence of carbohydrate (Cerebrosides, Globosides and Gangliosides and also Sulfatides) Thank You