Lipids PDF

Lipids: overview Lipids: heterogenous group actually or potentially related to fatty acids (long C-chain carboxylic acids, saturated or unsaturated) Main characteristics: - insoluble in H2O, soluble in non-polar solvents; - can self-assemble in water due to the hydrophobic eff...

Lipids: overview Lipids: heterogenous group actually or potentially related to fatty acids (long C-chain carboxylic acids, saturated or unsaturated) Main characteristics: - insoluble in H2O, soluble in non-polar solvents; - can self-assemble in water due to the hydrophobic effect forming bilayers, micelles, etc Role in organisms: - dietary: high energy value, source of vitamins and ☆ essential fatty acids (EFAs C-18 Linolenic (3 unsat) and Linoleic (2 unsat); main energy reserve of the organism - insulating material (adipose tissue- thermal insulator, also electrical insulator for nerves) - segregation and dynamic interface (membranes), transport, signaling (e.g. lipoproteins) 2  Lipids: derivatives of fatty acids Classification: 1. Simple Lipids: Esters of fatty acids (FA) with various alcohols Fats: Esters of FA with glycerol- liquid fats are oils; MP depends on % saturated fatty acid and on MW Waxes: Esters of FA with high molecular weight alcohol 2. Complex Lipids: Esters of FAs containing other groups in addition to an alcohol and a FA. Phospholipids Glycerophospholipids: alcohol is glycerol Sphingophospholipids: alcohol is sphingosine sugar, carbohydrates Glycolipids: contain a FA, sphingosine and carbohydrate Other complex Lipids: Lipoproteins 3. Precursor and derived lipids: FAs, steroids(C30), terpenes, glycerol (Neutral Lipids) 3  Fatty acids (FA) - long chain carboxylic acids; the natural ones usually have an even number of C atoms due to their biosynthesis (from C2 fragments, AcCoA) - saturated or unsaturated - shape and physicochemical characteristics dramatically changed: ☆☆ ↑ unsat Imp micelle ↑ sat ↑MP 4  * * essential * fatty acids ↳ preseasor of inflammation 4 pain 5  Unsaturated fatty acids - mono- or polyunsaturated fatty acids (PUFA) - nomenclature: chemists count from the carboxyl carbon (blue numbering), physiologists count from the omega (ω) carbon (red numbering): (c) 20:4(5,8,11,14) Eicosatetraenoic acid (Arachidonic acid) W-6 - Eicosanoic fatty acids (EFA), especially arachidonic acid, are important precursors of prostaglandins, leukotrienes, tromboxanes, prostacyclins – special lipids associated with inflammation and pain; 6  Unsaturated fatty acids - due to the presence of double bonds and its geometry they have low melting points – relevant to fluidity of membranes in which they are incorporated - can undergo oxidation (with endogenous peroxides, O2) generating rancidity, tissue damage; possible involvement of in cancer and inflammation - trans fatty acids are rare in nature; they are produced in small quantities during lipid metabolism and during the manufacture of liquid vegetable oils and margarine. They tend to cause an increase in plasma cholesterol levels. The FDA requires listing of trans-FA’s on food labels 7  Triacylglycerols (triglycerides, fats) - triesters of glycerol with fatty acids - fatty acid chains can be identical (e.g tripalmitin, tristearin) or different: - non-polar, water insoluble (the -COOH, -OH polar groups are condensed together) - lower density than water, excellent thermal and electrical insulation properties 8  Triacylglycerols - fatty acid distribution in various fats and oils: - energy storage role - can be hydrolyzed in basic medium or enzymatically (lipases) O O H 2C O R1 H 2C O H -O R1 O OH- O HC O R2 + 3 H 2O HC OH + -O R2 O O H 2C O R3 H 2C O H -O R3 9  Waxes (energy storage, water repellent materials, L-Glycerol 3-phosphate many with pharmaceutical, cosmetic uses) 10 Glycerophospholipids - general structure: - main components of cellular membranes Lecithins 11  Lecithins: surfactant properties - lecithins like dipalmitoyl phosphatidyl choline (DPPC or dipalmitoyl lecithin) are important as surfactants (surface active agents which decrease surface tension) without them neonates experience Respiratory Distress Syndrome (RDS). ☆ DPPC 12  Lipids with ether linkages - in vertebrate heart tissue (1/2 of the lipids are plasmalogens) - released from leukocytes (basophils); - stimulates platelet aggregation and release of choline serotonin (vasoconstrictor) - important role in inflammation and allergic response 13  Sphingolipids binnemes 14 Glycosphingolipids determine ABO blood types ☆ 15 Enzymatic degradation of phospholipids: specificity of phospholipases ☆ ☆ ☆ 16  Sterols - structural lipids, constituents of eukaryotic cell membrane; - characteristic steroid nucleus (almost planar, rigid) - Cholesterol (can dissolve - cholesterol is excreted as bile acids sterols)17  O CH2 O C R1 R2 C O C H O R2 C O C H O CH2 O P O Lipids: signaling role CH2 O P O O O O R2=Arachidonate H O =Arachidonate O O CH2 O C HR1 HO 1 6 O P O HO 1 6 O P O 2 OH O 5 O R2 C O C H O H 2 OH O 5 O CH2 O P HO H 3 4 H H O3 4 H H O H O R2=Arachidonate H O O P O O P1 6O O HO O 2 OH O 5 O H O P O Phosphatidylinositol 4,5-bisphosphate PIP 2 Phosphatidylinositol H 3 44,5-bisphosphate H (PIP2 ) ( ) O H O2PIP O O P O O P O O P O O H 2O O O O H 2O O H O O CH2 O C R1 H O Phosphatidylinositol 4,5-bisphosphate O CH O C R1 (PIP2 ) HO O P O2 R2 C O C H HO O O P O R2HOC OO C H OH + + CH2 OH O OHP OO O H H O H H 2O H H IP CH H Diacylglycerol O 2 OH O3 DAG Diacylglycerol (DAG) (DAG) H O H O (water-soluble, in cytoplasm) O CH2 O C R1 (intracellular messenger, remains attached O P O OHOP O O P O on the membrane) RO2 C O C H + OOHHO O CH2 OH Inositol 1,4,5-triphosphate H H Inositol 1,4,5-triphosphate (DAG) (IPDiacylglycerol 3) Activation of H (IP3)O Activation of Protein Kinase C O P O Protein Kinase C O Inositol 1,4,5-triphosphate Release of Ca++ Release of Ca++ (IP3) Activation of Enzyme Activation Enzyme Activation Hormone Protein Kinase C Hormone Enzyme Activity Enzyme Activity Activation Activation Release of Ca++ 18  Eicosanoids: paracrine hormones - paracrine hormones influence the environment around their synthesis site All molecules very lipophilic 19  Steroid hormones - Oxidized derivatives of sterols - Lack the alkyl chain attached to the D ring of cholesterol → more polar; move via blood from production site to target tissues → stimulate specific nuclear receptors Sex hormones (male/female): Hormones produced by adrenal cortex7(involved in glucose metabolism): stress hormone regulets BP - Synthetic steroids (antiinflammatory activity → management of asthma) 20  Vitamin D3 production and metabolism - vitamins: essential compounds that cannot be synthesized endogenously and have to be taken into food more active This is the active form of Vit D. It is available as Rocaltrol  tablets (Calcitriol) * - Rickets: lack of Vitamin D → demineralization of bone tissue: skeletal deformities, delayed growth, high risk of bone fracture, dental problems, muscle weakness - this vitamin is added to foods routinely 21 Isoprenoids: Vitamin A1, precursors and derivatives (milk, fish liver oil)  Visual pigment Hormone: development of epithelial tissue, skin → cosmetics 22  Other biologically-active isoprenoid compounds (tocopherol) 23  Goals and Objectives Upon completion of this lecture at minimum you should be able to answer the following: ►What are lipids, how are they classified, what are their main characteristics and physiologic roles? ►What are fatty acids, what is their nomenclature, how they self-assemble, where can they be found, which ones are essential, which representatives are phisiological relevant? ►What are triglycerides and waxes, what is their main role in organism, what relevant chemical reactions do they display? ►Which are the main structural and physiological/biological characteristics of glycerophospholipids? ►Which are the main structural and physiological/biological characteristics of sphingolipids? ►What implies the notion of phospholipase specificity? ►What is the physiologic impact of glycosphingolipids? ►What are sterols, and which are their main structural and physiological/biological characteristics? ►How can lipids/sterols and their derivatives/metabolites act in signaling cascades, as hormones and vitamins, and where? 24  Drugs and diseases ► Diseases: Respiratory Distress Syndrome (RDS) in neonates, thrombosis, inflammation, asthma, rickets ► Drugs and vitamins, supplements: synthetic DPPC, linoleic and linolenic acids, prednisone, prednisolone, vitamins A, D (Rocaltrol® tablets, (Calcitriol)), E, K 1, coenzyme Q, warfarin 25