Lipids PDF

LIPIDS JHON RAPHAEL M. JIMENEZ, RPh, MSPharm Pharmaceutical Biochemistry TOPIC OUTLINE I. Introduction II. Classification of Lipids III. Biological Membrane IV. Lipoproteins INTRODUCTION TO LIPIDS  Lipids are biomolecules that are soluble in organic solvents and insoluble in water.  They are...

LIPIDS JHON RAPHAEL M. JIMENEZ, RPh, MSPharm Pharmaceutical Biochemistry TOPIC OUTLINE I. Introduction II. Classification of Lipids III. Biological Membrane IV. Lipoproteins INTRODUCTION TO LIPIDS  Lipids are biomolecules that are soluble in organic solvents and insoluble in water.  They are not defined by a particular functional group, thus they have a variety of structures and functions.  They contain many nonpolar C-C and C-H bonds and few polar bonds resulting in their water insolubility. MAJOR ROLES OF BIOLOGICAL LIPIDS 1. They serve as structural components of biological membranes. (e.g. phospholipids) 2. They provide energy reserves, predominantly in the form of triacylglycerides. (9 kcal) 3. Both lipids and lipid derivatives serve as chemical messengers (e.g. vitamins and hormones) 4. Lipophilic bile acids aid in lipid solubilization. II. CLASSIFICATION OF LIPIDS LIPIDS  Lipids can be categorized as: 1. Hydrolyzable lipids can be converted into smaller molecules by hydrolysis. Hydrolyzable lipids Waxes Triacylglycerols Phospholipids LIPIDS  Lipids can be categorized as: 2. Non-hydrolysable lipids cannot be cleaved into smaller molecules by aqueous hydrolysis. Nonhydrolyzable lipids Fat-soluble Steroids Eicosanoids vitamins HYDROLYZABLE LIPIDS FATTY ACIDS  Hydrolyzable lipids are derived from fatty acids.  Fatty acids are carboxylic acids (RCOOH) with long C chains of 4-36 C atoms.  An example is CH3(CH2)14COOH (palmitic acid). Polar portion = hydrophilic Nonpolar portion = Lipophilic FATTY ACIDS  Naturally occurring fatty acids have an even number of C atoms.  Saturated fatty acids have no double bonds in their long hydrocarbon chains.  Unsaturated fatty acids have one (monounsaturated fatty acids) or more double bonds (polyunsaturated fatty acids), generally cis, in their long hydrocarbon chains.  As the number of double bonds in the fatty acid increases, the melting point decreases. FATTY ACIDS  Stearic acid (MP 71ºC) is a saturated fatty acid.  Oleic acid (MP 16ºC) is an unsaturated fatty acid. FATTY ACIDS NOMENCLATURE OF FATTY ACIDS  Simplified: Chain length : Double bonds (e.g. 16:0, 18:1)  # of carbonyl carbon : # of double bonds  Positions of any double bond: delta (△) - specified relative to C1 by a superscript number indicating the lower-numbered C in the double bond  Example: △9 NOMENCLATURE OF FATTY ACIDS  Omega-n Nomenclature: alternative nomenclature applied in human nutrition  n = the carbon at which the first double bond occurs in the carbon chain (beginning at the end of the chain containing methyl group)  Linolenic acid is called an omega-3 acid, because of the position of the first C=C in the nonpolar chain. FATTY ACIDS  Human require omega-3 linolenic acid  Essential Fatty Acid  Precursor in the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) WAXES  Waxes are esters formed from a fatty acid and a high molecular weight alcohol.  General structure of waxes:  General formation of waxes: WAXES  For example, shown below is the formation of spermaceti wax, isolated from the heads of sperm whales. WAXES  Because of their long nonpolar Carbon chains, waxes are very hydrophobic.  They form protective coatings on bird’s feathers and sheep’s wool and make up beeswax.  Beeswax (Myricyl palmitate) WAXES  Like other esters, waxes are hydrolyzed with water in the presence of acid or base to reform carboxylic acid and alcohol they came from. TRIACYLGLYCEROLS – FATS AND OILS  Triacylglycerols (Triglycerides) are three esters formed from glycerol and three molecules of fatty acids.  Below is a generalized block diagram of a triacylglycerol: TRIACYLGLYCEROLS – FATS AND OILS  The general reaction for the formation of triacylglycerol: TRIACYLGLYCEROLS – FATS AND OILS  General Features:  Simple triacylglycerols have three identical fatty acid side chains TRIACYLGLYCEROLS – FATS AND OILS  General Features:  Mixed triacylglycerols have two or three different fatty acid side chains TRIACYLGLYCEROLS – FATS AND OILS  General Features:  Saturated triacylglycerols contain only saturated fatty acids; they make up most animal fat and are solids at room temperature TRIACYLGLYCEROLS – FATS AND OILS  General Features:  Unsaturated triacylglycerols contain at least one unsaturated fatty acid; they make up most vegetable oils and are liquids at room temperature. TRIACYLGLYCEROLS – FATS AND OILS  General Features:  Unsaturated triacylglycerols contain at least one unsaturated fatty acid; they make up most vegetable oils and are liquids at room temperature.  Monosaturated triacylglycerols have one C=C bond.  Polyunsaturated triacylglycerols have many C=C bonds.  Increasing the number of double bonds in the fatty acid chain decreases the melting point of the triacylglycerol. TRIACYLGLYCEROLS – FATS AND OILS  An unsaturated triacylglycerol: TRIACYLGLYCEROLS – FATS AND OILS  Fats have higher melting points; they are solids at room temperature.  Fats are derived from fatty acids with few double bonds.  Oils have lower melting points; they are liquids at room temperature.  Oils are derived from fatty acids having a larger number of double bonds. FOCUS ON HEALTH AND MEDICINE FATS AND OILS IN DIET  Fats are used to build cell membranes, insulate the body, and store energy for later use.  It is recommended that no more than 20-35% of a person’s caloric intake should come from lipids.  A high intake of saturated triacylglycerols is linked to heart disease.  Saturated fats stimulate cholesterol synthesis, which can lead to cholesterol plaques building up inside arteries.  The result is high blood pressure, heart attack, and even stroke. FOCUS ON HEALTH AND MEDICINE FATS AND OILS IN DIET  Unsaturated triacylglycerols lower the risk of heart disease by decreasing the level of cholesterol in the blood.  Triacylglycerols formed from omega-3 fatty acids are very helpful in lowering the risk of heart attack.  However, if the double bond of the unsaturated triacylglycerol is trans, the beneficial effect is lost.  Trans fat, which are primarily synthesized instead of naturally occurring, act like saturated fats and increase the cholesterol levels in the blood. FOCUS ON HEALTH AND MEDICINE FATS AND OILS IN DIET HYDROLYSIS OF TRIACYLGLYCEROLS  Triacylglycerols are hydrolyzed with water in the presence of acid, base or enzymes (in the body). FOCUS ON THE HUMAN BODY METABOLISM OF TRIACYLGLYCEROLS  Human store energy as triacylglycerols in adipose cells below the surface of the skin, in the breast area and surrounding internal organs.  The number of adipose cells is constant; weight gained or lost causes them to swell or shrink, but not decrease or increase in number.  To metabolize triacylglycerols for energy, the esters are hydrolyzed by enzymes called lipases.  Complete metabolism of a triacylglycerol yields CO2, H2O, and a great deal of energy. PHOSPHOLIPIDS  Phospholipids are lipids that contain a P atom.  Two common types of phospholipids are phosphoacylglycerols and sphingomyelins. PHOSPHOLIPIDS PHOSPHOACYLGLYCEROLS  Phosphoacylglycerols are the main component of most cell membranes.  Structurally, they resemble a triacylglycerol, except the third fatty acid has been replaced with a phosphodiester bonded to an alcohol. PHOSPHOLIPIDS PHOSPHOACYLGLYCEROLS  The two fatty acid side chains form two nonpolar tails that lie parallel to each other.  The phosphodiester end of the molecule is a charged or polar head. FIVE TYPES OF PHOSPHOGLYCERIDES PHOSPHOLIPIDS PHOSPHOACYLGLYCEROLS  One of the main types of phosphoacylglycerols is cephalin: PHOSPHOLIPIDS PHOSPHOACYLGLYCEROLS  The second of the main types of phosphoacylglycerols is lecithin PHOSPHATIDYLCHOLINES (LECITHIN)  Phosphoacylglycerol containing choline  Most abundant phospholipids of the cell membrane and represent a large proportion of the body’s store of choline.  CHOLINE – important nervous transmission, as acetylcholine, and as a store of labile methyl group. PHOSPHATIDYLCHOLINES (LECITHIN)  DIPALMITOYL LECITHIN  Effective surface-active agent  Major constituent of the surfactant preventing adherence, due to surface tension of the inner surfaces of the lungs.  Absence: Respiratory distress syndrome  PHOSPHATIDYLETHANOLAMINE (Cephalin) and PHOSPHATIDYLSERINE (Tissues)  Ethanolamine or serine replaces choline PHOSPHATIDYLINOSITOL  Precursor of secondary messenger  Inositol is present as stereoisomer, myoinositol.  Phosphatidylinositol 4,5-biphosphate is an important constituent of the cell membrane phospholipids and cleaved into diacylglycerol (DAG) and inositol triphosphate (IP3), which are internal signals or second messenger. CARDIOLIPIN  Major lipid of mitochondrial membrane  LYOSPHOSPHOLIPIDS  Are intermediates in the metabolism of phosphoglycerols  Important in the metabolism and interconversions of phospholipids (Lysophosphatidylcholine)  Found in oxidized lipoproteins and can promote atherosclerosis PHOSPHOLIPIDS SPHINGOMEYLINS  Sphingomeylins do not contain a glycerol backbone, they have a sphingosine backbone instead.  Sphingomyelins do not contain an ester; their single fatty acid is bonded to the backbone by an amide bond. sphingosine PHOSPHOLIPIDS SPHINGOMEYLINS CERAMIDE  Sphingosine plus amino acid  Structure found in glycosphingolipids GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)  Distributed in every tissue of the body  Nervous tissues (brain)  Plasma membrane – cell surface carbohydrates  Glycosphingolipids  Major glycolipids in animal tissues  Ceramide + sugar  Galactoceramide  Major sphingolipid of brain and other nervous tissue, C24 fatty acids GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)  GANGLIOSIDES  Are complex glycosphingolipids derived from glucosylceramide that contain in addition one or more molecules of a sialic acid  NEURAMIDIC ACID – principal sialic acid found in human tissues  GM3 – contains ceramide, one molecule of glucose, one molecule of galactose and one molecule of NeuAc  The simplest gangliosides in tissues  SUMMARY Waxes 1 Fatty Acid Triacylglycerols 3 Fatty Acids Hydrolysable Phosphoacylgyce 2 Fatty Acids rols Phospholipids Sphingomyelins 1 Fatty Acid NON-HYDROLYZABLE LIPIDS FOCUS ON HEALTH AND MEDICINE CHOLESTEROL  Steroids are a group of lipids whose carbon skeletons contain several fused rings. FOCUS ON HEALTH AND MEDICINE CHOLESTEROL  Cholesterol, the most prominent steroid, is synthesized in the liver and found in almost all body tissues.  It is obtained in the diet from many sources including meat, cheese, butter, eggs. cholesterol STEROID HORMONES  A hormone is a molecule that is synthesized in one part of an organism, which then elicits a response at a different site.  Two important classes of steroid hormones include sex hormones and adrenal cortical steroids.  The female sex hormones are estrogens and progestins.  The male sex hormones are called androgens. STEROID HORMONES FEMALE SEX HORMONES: ESTROGENS  The estrogens (estradiol and estrone) control development of secondary sex characteristics, regulate the menstrual cycle, and are made in the ovaries. STEROID HORMONES FEMALE SEX HORMONES: PROGESTIN  The progestin progesterone is called the “pregnancy hormone”. It is responsible for the preparation of the uterus for implantation of a fertilized egg. STEROID HORMONES MALE SEX HORMONES: ANDROGENS  Testosterone and androsterone are androgens made in the testes.  They control the development of secondary sex characteristics in males. STEROID HORMONES ANABOLIC STEROIDS  Synthetic androgen analogues called anabolic steroids, promote muscle growth.  They have the same effect as testosterone, but are more stable, so they are not metabolized as quickly.  They have come to be used by athletes and body builders but are not permitted in competitive sports. STEROID HORMONES ANABOLIC STEROIDS STEROID HORMONES ADRENAL CORTICAL STEROIDS  Three examples of adrenal cortical steroids are: aldosterone cortisone cortisol STEROID HORMONES ADRENAL CORTICAL STEROIDS  Aldosterone regulates blood pressure and volume by controlling the concentration of Na+ and K+ in body fluids.  Cortisone and cortisol serve as anti-inflammatory agents, which also regulate carbohydrate metabolism (Catabolic effects).  Prolonged use of these steroids can have undesired effects, including bone loss (osteoporosis) and high blood pressure.  Prednisone, a synthetic alternative, has similar anti- inflammatory properties. FOCUS ON HEALTH AND MEDICINE FAT-SOLUBLE VITAMINS  Vitamins are organic compounds required in small quantities for normal metabolism and must be obtained from the diet.  Vitamins are either water-soluble or fat- soluble.  The four fat-soluble vitamins (A, D, E, and K) are found in fruits, vegetables, fish, liver, and dairy products.  They are stored in adipose cells to be used when needed. FOCUS ON HEALTH AND MEDICINE FAT-SOLUBLE VITAMINS  Vitamin A is found in liver, fish, and dairy products and is made from B-carotene.  It is needed for vision and for healthy mucous membranes.  Vitamin A deficiency causes night blindness and dry eyes and skin. FOCUS ON HEALTH AND MEDICINE FAT-SOLUBLE VITAMINS  Vitamin D can be synthesized from cholesterol.  It can be obtained in the diet from many foods, especially milk, and helps regulate Ca and K metabolism.  A deficiency of Vitamin D causes rickets (bone malformation), osteomalacia in adults. FOCUS ON HEALTH AND MEDICINE FAT-SOLUBLE VITAMINS  Vitamin E is an antioxidant, protecting unsaturated side chains in fatty acids from unwanted oxidation.  Deficiency of Vitamin E causes numerous neurological problems, although it is rare. FOCUS ON HEALTH AND MEDICINE FAT-SOLUBLE VITAMINS  Vitamin K regulates the synthesis of clotting proteins (prothrombin), and deficiency of this leads to excessive or fatal bleeding.  Sources can be found in cabbage, pechay, spinach. FOCUS ON HEALTH AND MEDICINE PROSTAGLANDINS AND LEUKOTRIENES  Prostaglandins and leukotrienes are two types of eicosanoids.  All eicosanoids are very potent compounds, which are not stored in cells, but rather synthesized in response to external stimulus.  Unlike hormones, they are local mediators, performing their function in the environment in which they are synthesized. FOCUS ON HEALTH AND MEDICINE PROSTAGLANDINS  Prostaglandins are carboxylic acids that contain a five-membered ring and have a wide range of biological activities. FOCUS ON HEALTH AND MEDICINE PROSTAGLANDINS  Prostaglandins are responsible for inflammation.  Aspirin and ibuprofen relieve pain and inflammation by blocking the synthesis of these molecules.  Prostaglandins also decrease gastric secretions, inhibit blood platelet aggregation, stimulate uterine contraction, and relax smooth muscles.  There are two different cyclooxygenase enzymes responsible for prostaglandin synthesis called COX-1 and COX-2. FOCUS ON HEALTH AND MEDICINE PROSTAGLANDINS  COX-1 is involved in the usual production of prostaglandins.  COX-2 is responsible for additional prostaglandins in inflammatory diseases like arthritis.  Nonsteroidal anti-inflammatory drugs (NSAIDS) like aspirin and ibuprofen inactivate both COX-1 and COX-2, but increase risk for stomach ulcer formation.  Drugs sold as Vioxx, Bextra, and Celebrex block only the COX-2 enzyme without affecting gastric secretions. FOCUS ON HEALTH AND MEDICINE ASTHMA AND LEUKOTRIENES  Asthma is characterized by chronic inflammation, so inhaled steroids to reduce this inflammation are commonly used.  Leukotrienes are molecules that contribute to the asthmatic response by constricting smooth muscle of the lung.  New asthma drugs act by blocking the synthesis of leukotriene C4, which treat the disease instead of just the inflammation symptoms. IV. LIPOPROTEINS CLASSIFICATION OF LIPOPROTEINS 1. Chylomicrons 2. Very Low-Density Lipoproteins (VLDL) 3. Intermediate-Density Lipoproteins (IDL) 4. Low-Density Lipoproteins (LDL) 5. High-Density Lipoproteins (HDL)