8. LIPIDS AND LIPID METABOLISM.pdf

LIPIDS COMPILED AND ARRANGED BY JUSTIN RACHELLE P. DIMAGUIBA  LEARNING OUTCOMES Describe the biochemical and physiological functions of lipids. Trace the metabolism of lipids in the human body. Relate the role of the liver to lipid metabolism.  Lipids Organic mol...

LIPIDS COMPILED AND ARRANGED BY JUSTIN RACHELLE P. DIMAGUIBA  LEARNING OUTCOMES Describe the biochemical and physiological functions of lipids. Trace the metabolism of lipids in the human body. Relate the role of the liver to lipid metabolism.  Lipids Organic molecules characterized by their solubility in non polar solvents such as ether, chloroform, and acetone hydrophobic Function as energy storage, protection of organs, insulation, and absorption of vitamins Others are energy sources, hormones or vitamins  Properties of Lipids Lipids may be either liquids or non-crystalline solids at room temperature. Pure fats and oils are colorless, odorless, and tasteless. energy-rich organic molecules Insoluble in water Soluble in organic solvents like alcohol, chloroform, acetone, benzene, etc. No ionic charge Solid triglycerols (Fats) have high proportions of saturated fatty acids. Liquid triglycerols (Oils) have high proportions of unsaturated fatty acids.  Function of Lipids 1. Serves as hormones and hormone precursors 2. Aids in digestion 3. Provides energy storage and metabolic fuels 4. Acts as functional and structural components of biomembranes 5. Forms insulation to allow nerve conduction or to prevent heat loss  Structure of Lipids made of the elements Carbon, Hydrogen and Oxygen, but have a much lower proportion of water than other molecules such as carbohydrates Unlike polysaccharides and proteins, lipids are not polymers—they lack a repeating monomeric unit. They are made from two molecules: Glycerol and Fatty Acids Structure of Lipids  Structure of Lipids A glycerol molecule is made up of three carbon atoms with a hydroxyl group attached to it and hydrogen atoms occupying the remaining positions. Fatty acids consist of an acid group at one end of the molecule and a hydrocarbon chain, which is usually denoted by the letter ‘R’. They may be saturated or unsaturated. A fatty acid is saturated if every possible bond is made with a Hydrogen atom, such that there exist no C=C bonds.  Saturated FAs A fatty acid is saturated if every possible bond is made with a Hydrogen atom, such that there exist no C=C bonds.  Unsaturated FAs Unsaturated fatty acids, on the other hand, do contain C=C bonds. Monounsaturated fatty acids have one C=C bond, and polyunsaturated have more than one C=C bond. Structure of Triglycerides Triglycerides are lipids consisting of one glycerol molecule bonded with three fatty acid molecules. bonds between the molecules are covalent and are called ester bonds They are formed during a condensation reaction. The charges are evenly distributed around the molecule so hydrogen bonds to not form with water molecules making them insoluble in water. Structure of Triglycerides Classification of Lipids  Simple Lipids Esters of fatty acids with various alcohols: a) Neutral fats (Triacylglycerol, TG): These are tri-esters of fatty acids with glycerol. b) Waxes are esters of fatty acids with higher monohydroxy aliphatic alcohols. True waxes are esters of higher fatty acids with cetyl alcohol (C16H33OH) or other higher straight chain alcohols. Cholesterol esters are esters of fatty acid with cholesterol. Vit A and Vit D esters are palmitic or stearic acids esters of Vit A (Retinol) or Vit D respectively.  Compound Lipids Esters of fatty acids containing groups, other than, and in addition, to an alcohol and fatty acids. a) Phospholipids: They are found chiefly in animal tissues. They are substituted fats containing in addition to fatty acid and glycerol, a phosphoric acid residue, a nitrogenous base and other substituents. Examples of Phospholipids Phospholipids (Phosphatides): They are found chiefly in animal tissues. Substituted fats, consisting of phosphatidic acid; composed of glycerol, fatty acids and phosphoric acid found in ester linkage to a nitrogenous base. Examples of Phospholipids Lecithin: Lecithin is found in brain, egg yolk and organ meats. Phosphatidyl choline or serine—phosphatide linked to choline; a lipotropic agent; important in fat metabolism and transport— are used as emulsifying agent in the food industry. Examples of Phospholipids Cephalin: Occurs predominantly in nervous tissue. Phosphatidyl ethanolamine; phosphatide linkage to serine or ethanolamine. Examples of Phospholipids Plasmalogen: They are found in brain, heart and muscle. Examples of Phospholipids Lipositol: They are found in brain, heart, kidneys and plant tissues together with phytic acid. Phosphatidyl inositol means phosphatide linked to inositol. Their rapid synthesis and degradation takes place in brain. Examples of Phospholipids Sphingomyelin: They are found in nervous tissue, brain and red blood cells. Sphingosine containing phosphatide; yields fatty acids, choline, sphingosine, phosphoric acid and no glycerol.  Compound Lipids b) Glycolipids: Lipids containing carbohydrate moiety are called glycolipids. They contain a special alcohol called sphingosine or sphingol and nitrogenous base in addition to fatty acids but does not contain phosphoric acid or glycerol. Examples of Glycolipids Cerebroside or Glycolipid or Glycosphingosides: They are found in myeline sheaths of nerves, brain and other tissues. They upon hydrolysis yields sphingosine, galactose (or glucose) and fatty acids. Examples of Glycolipids Ganglioside: Found in the brain, nerve tissue and other selected tissues, notably spleen. They contain a ceramide linked to hexose (glucose or galactose), neuraminic acid, sphingosine and fatty acids. Examples of Glycolipids Sulfolipid: They are found in white matter of brain, liver and testicle, also found in plant chloroplast. They are sulphur-containing glycolipid. In sulfolipid, sulphate is present in ester linkage to galactose. Examples of Glycolipids Aminolipids (Proteolipids): They are found in brain and nerve tissue. They are the complexes of protein and lipids.  Derived Lipids Hydrolysis product of simple and compound lipids is called derived lipids. They include fatty acid, glycerol, sphingosine and steroid derivatives. Derivatives obtained by hydrolysis of those given in group I and II, which still possess the general characteristics of lipids. a) Fatty acids may be saturated, unsaturated or cyclic. b) Monoglycerides (monoacylglycerol) and Diglycerides (diacylglycerol) c) Alcohols Examples of Derived Lipids Eicosanoids are signalling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, 20 carbon units in length. Examples of Derived Lipids Eicosanoids Most eicosanoids are produced from arachidonic acid, which is a polyunsaturated fatty acid that you get from eating foods like animal fats. They have many effects on your body, including inflammation, fever promotion, blood pressure regulation, and blood clotting. Three classes of eicosanoids There are three classes of eicosanoids: prostaglandins, thromboxane, and leukotrienes. various eicosanoids are produced in different cell types by different synthetic pathways, and have different target cells and biological actions.  Miscellaneous Lipids Aliphatic hydrocarbons – iso-octadecane from liver Squalene – hydrocarbons in shark liver and human sebum Carotenoids Vitamin D, E and K  Fats They are neutral ester of monobasic fatty acids with trihydric alcohol, glycerol.  Types of Fats Animal fat – contains mostly oleic, palmitic, and stearic acids Mutton fat – has more stearic and less oleic than pork Butter fat – composed mainly of palmitic and oleic acids with small amount of butyric acid and caproic acid Human fat – mostly oleic acid; has a yellowish tinge due to carotene and xanthophylls pigments derived from the ingested food  Fatty Acids These are products of fat hydrolysis. They occur in plant and animal foods also exhibit in complex forms with other substances Fatty acids usually contain an even number of carbon atoms and are straight chain derivatives. Classification of Fatty Acids  Nomenclature of Fatty Acids Saturated fatty acids PREFIX: # of hydrocarbons SUFFIX: -anoic Ex: 1. Capric acid (C-10)= decanoic acid 2. Palmitic acid (C-16)= hexadecanoic acid  Nomenclature of Fatty Acids Polyunsaturated fatty acids PREFIX: # of hydrocarbons SUFFIX: -enoic (1 double bond), dienoic( 2 double bonds), etc Ex: 1. Linoleic acid (C-18:2)= cis, cis-9,12,-octadecadienoic acid 2. Gamma-Linolenic acid (18:3) 6,9,12-octadecadatrieonic acid  Trivial names contain no clues to the structures one must learn the name and associate it with a separately learned structure names typically derive from a common source of the compound or the source from which it was first isolated EX: palmitic acid is found in palm oil oleic acid is a major constituent of olive oil (oleum) stearic (from the Greek word meaning solid) acid is solid at room temperature Spiders (arachnids) contain arachidonic acid  Greek letters denote positions relative to the carboxyl carbon Building Blocks: Fatty Acids a carboxylic acid either saturated, or unsaturated a vital constituent of lipids and is released during fasting from triacylglycerols to accommodate the energy requirements of the body Fatty Acid Structure  Types of fatty acids Based on carbon chain length a. Long-chain fatty acid (C-12 to C-26) b. Medium chain fatty acid (C-8 and C-10) c. Short-chain fatty acid (C-4 and C-6) Types of fatty acids Based on carbon to carbon bonds a. Saturated fatty acids (SFAs) b. Monounsaturated fatty acids (MUFAs) c. Polyunsaturated fatty acids (PUFAs)  Examples of Unsaturated Fatty Acid In its symbols form First no. represent C numbers and Second no. represent the double bond. Greek letter delta( ) signifies double bond. Types of fatty acids Fatty acids with carbon-carbon double bond are unsaturated. Saturated fatty acids lack this double carbon bonding.  Saturated Fatty Acids fatty acids have a single C-C bond solid at room temperature usually contain 12-22 carbon atoms Ex: Ghee, Butter, Palmito-oleic acid etc.  Saturated Fatty Acids These belong to the acetic series and have the general formula of CnH2nO2 Palmitic acid make up about 15 to 50% of the total fatty acids in fats. Myristic and stearic acids are also present Tuberculo- stearic (10-methyl stearic acid) acid occurs in the lipids of human tubercle bacilli They are abundant in butter, animal fat, lard, coconut and peanut oil  Monounsaturated fatty acid fatty acids that have one double bond in the fatty acid chain with all of the remainder carbon atoms being single-bonded typically liquid at room temperature but start to turn solid when chilled EX: Olive oil, canola oil, peanut oil, safflower oil and sesame oil.  Monounsaturated fatty acid can help reduce bad cholesterol levels in the blood Lowers the risk of heart disease and stroke provides nutrients to help develop and maintain body’s cells. contribute vitamin E to the diet, an antioxidant vitamin  Polyunsaturated fatty acids contain more than one double bond in their backbone includes many important compounds, such as essential fatty acids give drying oils their characteristic property.  Polyunsaturated fatty acids can help reduce bad cholesterol levels in the blood which can lower your risk of heart disease and stroke Oils rich in polyunsaturated fats also provide essential fats that your body needs but can't produce itself – such as omega-6 and omega-3 fatty acids.  Polyunsaturated fatty acids Linoleic acid series (18 : 2; 9, 12) It contains two double bonds between C9 and C10; and between C12 and C13. Their general formula is CnH2n–3 COOH. Dietary sources: Linoleic acid is present in sufficient amounts in peanut oil, corn oil, cottonseed oil, soyabean oil and egg yolk  Polyunsaturated fatty acids Linolenic acid series (18 : 3; 9, 12, 15): It contains three double bonds between 9 and 10; 12 and 13; and 15 and 16. Their general formula is CnH2n–5 COOH. Dietary Source: Found frequently with linoleic acid, but particularly present in linseed oil, rapeseed oil, soybean oil, fish visceras and liver oil (cod liver oil).  Polyunsaturated fatty acids Arachidonic acid series (20 : 4; 5, 8, 11, 14): It contains four double bonds. Their general formula: CnH2n–7 COOH Dietary source: Found in small quantities with linoleic acid and linolenic acid but particularly found in peanut oil. Also found in animal fats including Liver fats.  Unsaturated Fatty acids have the Double C-C bond are LIQUID at room temperature If one double bond present in fatty acid it is called Monosaturated or Monoenoic fatty acids. If more than one double bond present in fatty acid it is called Polysaturated or Polyenoic fatty acid. For e.g. vegetable oil. Omega-3 polyunsaturated fatty acids found in oil from certain types of fish, vegetables, and other plant sources not made by the body and must be consumed in the diet are used together with diet and exercise to help lower triglyceride levels in the blood.  Omega-6 polyunsaturated fatty acids are used for reducing the risk of heart disease lower total cholesterol levels, lowering "bad" (LDL) cholesterol levels raising "good" (HDL) cholesterol levels Reduce the risk of cancer Omega-6 polyunsaturated fatty acids family of polyunsaturated fatty acids that have in common a final carbon-carbon double bond in the n-6 position the sixth bond, counting from the methyl end.  ESSENTIAL FATTY ACIDS Three polyunsaturated fatty acids, linoleic acid, linolenic acid and arachidonic acid are called “essential fatty acids” (EFA). cannot be synthesized in the body and must be provided in the diet Lack of EFA in the diet can produce growth retardation and other deficiency manifestation symptoms. Linoleic acid is most important as, arachidonic acid can be synthesized from linoleic acid by a three-stage reaction by addition of acetyl-CoA. Pyridoxal phosphate is necessary for this conversion. Biologically arachidonic acid is very important as it is precursor from which prostaglandins and leukotrienes are synthesized in the body.  Hydrogenation Hydrogenation of liquid vegetable fats is done commercially to obtain solidified fats like “margarine.  Trans Fatty Acid Overview one sub-type of fatty acid referred to trans fatty acids simply as trans fats helps preserve the shelf life of food To create a trans fat, an unsaturated fatty acid and force hydrogen ions in it, under high pressure  Health Effects of Trans Fats association between consumption of trans fats and heart disease no physiological need for the consumption of trans fats Trans fats occur in nature only to a small degree (and these may in fact be healthy) avoid manufactured trans fats partially hydrogenated oil on the label, there is trans fat in the product. hydrogenated soybean oil, not a healthy fat Manufacturers are now required to list the grams of trans fat on the label, but manufacturers can write 0 grams on the nutrition facts panel, even if there is 0.5 gram of trans fat. To figure out if a product has trans fat, look for partially hydrogenated and hydrogenated oil on the ingredient list.  Lipid Metabolism Role of the LIVER in Lipid Metabolism Excess protein and carbohydrates are converted into triglycerides Elimination of cholesterol and phospholipids in bile Synthesis of cholesterol and phospholipids Modification of cholesterol and triglycerides to produce water-soluble lipoproteins for transport to other body tissues  Absorptive State Liver converts glucose into fatty acids Retrieves fatty acids from lipids supplied with chylomicrons Fatty acids converted into neutral fats and phospholipids, VLDL formed Absorption if Lipids by enterocytes  Post-resorptive State Adipose tissue releases fatty acids Fatty acids taken up by liver and oxidatively degraded to acetyl coA Acetyl coA is converted into ketone bodies Fatty acid Activation Transport of FAs in the mitochondria  Transport of FAs in the mitochondria Steps i. Carnitine acyl transferase I (CAT I) present on outer surface of inner mitochondrial membrane transfers acyl group to carnitine. ii. Acyl carnitine is transported across the membrane to mitochondrial matrix by carrier protein translocase iii. CAT II found on the inner surface of inner membrane converts acyl carnitine to acyl CoA. iv. Carnitine released returns to cytosol for reuse  Beta-oxidation Proper Subcellular site: Mitochondrial matrix Involves four steps: i. Oxidation ii. Hydration iii. Oxidation iv. Thiolytic cleavage Beta-oxidation Proper Energetics of Palmitic acid oxidation Regulation of Beta-oxidation  Mobilization of Fats GLUCAGON G protein perilipin hormone coupled receptor CGI GTP EPINEPHRINE NOREPINEPHRINE Adenylate pKA cyclase ATP cAMP  Mobilization of Fats GLUCAGON G protein perilipin horm coupled one receptor GTP EPINEPHRINE CGI NOREPINEPHRINE Adenylate pKA cyclase ATP cAMP  Mobilization of Fats GLUCAGON G protein perilipin hormone coupled receptor GTP EPINEPHRINE CGI NOREPINEPHRINE Adenylate pKA cyclase ATP cAMP  Mobilization of Fats GLUCAGON G protein perilipin horm coupled one receptor GTP EPINEPHRINE CG I NOREPINEPHRIN Adenylate pKA E cyclase ATP cAMP Mobilization of Fats GLUCAGON G protein perilipin horm coupled one receptor GTP EPINEPHRINE CG I NOREPINEPHRINE Adenylate pKA cyclase ATP cAMP Gluconeogenesis ATP formation Albumin Activation Palmitoleic Acid CoA Fatty Acyl CoA Synthetase ATP Fatty Acyl CoA ADP Transport Fatty Acyl CoA CoA Carnitine Acyl Transferase type 1 Carnitine Carnitine Acyl Transferase type 2 Fatty Acyl Carnitine CoA Carnitine Fatty Acyl CoA  Beta oxidation Fatty Acyl CoA Acyl CoA Dehydrogenase FAD Trans delta 2 Enoyl CoA FADH Enoyl CoA 2 Hydratase H2O Beta Hydroxy acyl CoA Beta keto acyl CoA Acetyl Coa Beta ketoacyl CoA Thiolase Dehydrogenase NADH CoA NAD + Acetyl Coa  Ketogenesis Occurs in the mitochondria of liver cells Happens in prolonged starvation, low blood glucose, uncontrolled diabetes mellitus type 1, and carbohydrate restricting diets Ketones can enter the blood brain barrier and can be used as energy by the brain KETOLYSIS happens in the brain and muscles  Glucose Pyruvate Acetyl CoA  BETAOXIDATION Glucose Pyruvate Acetyl CoA ATP  BETAOXIDATION Glucose Pyruvate Acetyl CoA ATP GLUCONEOGENESIS GLUCONEOGENESIS MALAT E mi t o c h o n d r i a GLUCONEOGENESIS MALATE oxaloacetate m i t Phosphoenol o c pyruvate h o n d r GLUCOSE i a BETAOXIDATION m i t o c h o n d r i a  Thiolase CoA Aceto Acetyl CoA betahydroxybutarate HMG CoA Betahydroxybutarate Synthetase dehydrogenase CoA NAD Rate limiting HMG CoA H enzyme NAD+ HMG CoA Lyase Acetoacetate  H+ H+ H+ betahydroxybutarate H+ H+ Area postrema Vomiting Is triggered ketonuria Acetone Keto Acetoacetate breath acidosis (4C) Acetone (3C) hypovolemia -C Acetoacetate comatose Kussmaul decarboxylase breathing  betahydroxybutarat e Betahydroxybutarat e dehydrogenase NAD+ NAD H CoA Acetoacetate Aceto Acetyl Acetyl CoA (4C) CoA Acetyl CoA Thiophorase Acetyl CoA acyl transferase CoA  The link below is provided to summarized the discussion on lipid metabolism: https://www.youtube.com/watch?v=ppqpUVaasNc&t=54s Resource Parrocha-Abyadang, M.D. (2021). Module 5 Unit 2 Biochemistry in Nursing, SLU, SoNAHBS End of presentation