Biochemistry Tutorial 8: Lipids Structure & Classification PDF

Biochemistry – Winter 2024/1 Tutorial 8: Lipids Structue & Classification Nourhan Ihab Elfar, PhD Nihal Moustafa Mansour, PhD Assistant Professor of Biochemistry Assistant Professor of Biochemistry [email protected]...

Biochemistry – Winter 2024/1 Tutorial 8: Lipids Structue & Classification Nourhan Ihab Elfar, PhD Nihal Moustafa Mansour, PhD Assistant Professor of Biochemistry Assistant Professor of Biochemistry [email protected] [email protected] Mohamed Mohamed Naguib, PhD Assistant Professor of Biochemistry [email protected] Tutorial 8 November 6, 2024  Tutorial-4 Contents I. Introduction on Lipids : ✓ Definition. ✓ Solubility: Hydrophobic & Amphipathic Natures. II. Importance of Lipids : ✓ Lipids Vs. Carbohydrates as Energy Source. III. Fatty Acids : Building Blocks ✓ Saturated Vs. Unsaturated Fatty Acids. IV. General Classification : ✓ Simple, Compound, & Derived Lipids. V. Common Examples : ✓ Simple Lipids: Triacylglycerol (TAGs). ✓ Compound Lipids: Phospholipids & Glycolipids. ✓ Derived Lipids: Cholesterol. 2 Lipids: The Second Class of Biomolecules II Lipids (Fats) 3  I. Lipids: Definition & Solubility ❑ Definition: “Lipids are organic compounds that contain hydrogen, carbon, and oxygen atoms, which form the framework for the structure and function of living cells.” ❑ Solubility: A- Hydrophobic Nature: “These organic compounds are nonpolar hydrophobic molecules, which are soluble only in nonpolar solvents (alcohol, chloroform, benzene, etc.) and insoluble in water because water is a polar molecule”. The hydrophobic nature of lipids stems from the many nonpolar covalent bonds. Water, on the other hand, has polar covalent bonds and mixes well only with other polar or charged compounds. 4  I. Lipids: Definition & Solubility B- Amphipathic Natue: ✓ Amphipathic (or Amphiphilic) Nature of Lipids—that is, they have a hydrophilic (“water-loving”) or polar end (head) and a hydrophobic (“water-fearing”) or nonpolar end (tail). Examples: ✓ Phospholipids are specialized lipids that are partially soluble in water. This dual nature allows them to form structures called membranes which surround all living cells. All of the lipid molecules in cell membranes (phosphoipids) are amphipathic. ✓ Glycolipids. ✓ Cholesterol. 5  II. Importance of Lipids 1. Important Storage Form of Energy (Mainly TAGs). They give 9 Calories/ gram. 2. Structural Components: Important Constituents of Cell Membranes. 3. Help in Absorption of Fat Soluble Vitamins (A, D, E, and K). 4. Precursor for vitamin D synthesis (From cholesterol). 4. Important Constituent of Nervous Tissue. 5. Serve as a Thermal Insulator in the Subcutaneous Tissues. 6. Essential for Maintaining Cellular Integrity. 7. Act as Metabolic Regulators (Steroid Hormones) & Emulsifying Agents (Amphipathic Lipids). 6  II. Importance of Lipids: Lipids Vs. Carbohydrates as energy source Q; Why lipids (TAG; Triacylglycerol) is chosen , other than carbohydrates (glycogen), by our body as a fuel reserve during growth ? Answer: TAG stores allow survival for several weeks. While, glycogen sustain physiological function for about 24 hours due to the following criteria. Lipids Stores Carbohydrates Stores  III. Fatty Acids: Building Blocks ❑ Definition: ✓ Fatty acid is the building block of lipids. It is made from carboxylic group (-COOH) and hydrocarbon chain (-R). ❑ Classification: ✓ Fatty acids are classified into: 1. Saturated F.As (with single bonds only). 2. Unsaturated F.As (with at least one double bonds), that is further classified into Mono- and Poly- Unsaturated F.As according to the number of double bonds between carbon atoms. 8  IV. Classification of Fatty Acids ❑ According to the presence of double bonds (degree of unsaturation): 9  IV. Classification of Fatty Acids ❑ ∆n (indicate the position of the double bond) where n is the lower numbered carbon in the double bonded pair. ❑ The double bonds of polyunsaturated fatty acids are separated by CH2 (methylene) group so, they are not conjugated. ❑ The configuration of the double bonds in fatty acids is cis- (Same direction). ❑ The length of the hydrocarbon chain of a fatty acid and its degree of unsaturation affects the melting point. A). as number of carbon increases, the melting point increases (solid at room temperature). B). as the number of double bonds increases, the melting point decreases (liquid at room temperature). 10  Fatty Acids: Saturated Vs. Unsaturated Vs. 3 Structure I. State II. Health Unhealthy Fats: Increase the risk for coronary heart Healthier Fats: Decrease the risk for coronary heart III. disease. disease. 11  IV. Classification of Fatty Acids ❑ According to the nutritional importance (Biological classification): ω carbon is the carbon atom at the end of the hydrocarbon chain of a fatty acid. Nomenclature of unsaturated fatty acids with respect to ω carbon is as follows: [Number of carbons in the hydrocarbon chain of the fatty acid – Position of the last double bond in the fatty acid]. 12  V. General Classification of Lipids F.A.+ Alcohol + Possess F.A.+ Alcohol Results from Additional group characteristics of hydrolysis of lipids simple or compound lipids Cholesterol 13  VI. Common Examples-Simple Lipids ✓ Among simple lipids, two common examples are TAGs & Waxes. ❑ Triacylglycerol (TAGs) Esters of fatty acids with glycerol. Neutal fat. Most of edible fats are TAGs. Fat in liquid state is called Oil. ** Function of TAGs: TAGs are primarily stored in adipose tissue and serves as main energy storage. TAG is not a constituent of cell Structure of Triacylglycerol membrane as it lacks polar head groups. (TAG) 14  VI. Common Examples-Simple Lipids ❑ Fats and Oils that are widely distributed in both plant and animal tissues are chemically Triacylglycerols (TAGs). Liquid TAGs Solid TAGs 15  VI. Common Examples- Compound Lipids ✓ Among compound lipids, two common examples are Phospholipids & Glycolipids. A. Phospholipids: ▪ General Structure: F.A. + Alcohol + ▪ Classification: According to alcohol Phosphoric acid + Nitrogenous base (NB) present, it is further classified into Glycerophospholipids & Sphingophospholipids. 16  VI. Common Examples- Compound Lipids Phospholipids Importance 1. Major Lipid Constituents of Cellular Membranes and Myelin Sheath. 2. Serve as Good Emulsifying Agents and Help in Intestinal Absorption of Lipids. 3. Important Constituent of Lipoproteins. 17 VI. Common Examples- Compound Lipids B. Glycolipids: ▪ General Structure: ▪ Classification: According to carbohydrate present, (F.A. + Sphingosine) it is further classified into cerebrosides & Ceramide + gangliosides. Carbohydrate Cerebrocides Gangliosides (Simple) (Complex) 18  VI. Common Examples- Compound Lipids Cerebrosides (Simple Glycolipids) ✓ It acts as precursors for synthesis of more complex glycolipids (Gangliosides). ✓ According to the CHO moiety present it is divided into: a. Galactocerebrosides is found in high concentration in nerve tissue membrane. b. Glucocerebrosides is found in non-neural tissues. 19 VI. Common Examples- Compound Lipids Cerebrosides Vs. Gangliosides 20  VI. Common Examples- Compound Lipids Glycolipids Importance 1. Important constituent of cell membrane and nervous tissue (brain) in the body. 2. Constituents of cell surface receptors. 3. Have been identified as a source of blood group antigens. 21  VI. Common Examples- Derived Lipids ✓ Derived lipids include cholesterol, steroids, and prostaglandins etc... ❑ Cholesterol ❑ General Structure ✓ Cholesterol, a class of steroid containing 27-carbon atoms. ✓ The steroid nucleus consists of three six-membered rings (Phenantherene; rings A, B, and C) attached to one five-membered D- Cyclopentano-perhydro- ring (Cyclopentane). Phenatherene (CPPP) 22  VI. Common Examples- Derived Lipids Cholesterol Importance Cholesterol 1. Structural constituent of cell membranes and plasma lipoproteins. 1. Precursor for Steroid Hormones including; * Glucocorticoids (e.g. Cortisol). * Mineralocorticoids (e.g. ADH). * Androgens (male sex hormones). * Estrogens (Female sex hormones). * Progesterone. 3. Precursor for Vitamin D, that is essential for calcium & phosphate metabolism. 3. Precursor for Bile Salts/Acids, that emulsify dairy fats. 23 THE END  Biochemistry – Winter 2024/1 Tutorial 7: Lipids Digestion, Absorption & Transport Nourhan Ihab Elfar, PhD Nihal Moustafa Mansour, PhD Assistant Professor of Biochemistry Assistant Professor of Biochemistry [email protected] [email protected] Mohamed Mohamed Naguib, PhD Assistant Professor of Biochemistry [email protected] Tutorial 7 November 6, 2024  Tutorial 7 Contents I. Dietary Sources of Lipids : ✓ Animal & Vegetable Sources. II. Types of Dietary Lipids Undergoing Digestion. III. Digestion of Lipids (3 Stages) : ✓ Mouth, Stomach & Small Intestine (Pancreatic Juice). IV. Absorption of Lipids : ✓ Assembly of Chylomicrons. V. Clinical Significance : Defect in Digestion & Absorption of Lipids ✓ Lipid Malabsorption: Steatorrhea. VI. Transportation of Lipids : Lipoproteins ✓ Definition, Importance & Structure of Lipoproteins. ✓ Exogenous & Endogenous Pathways: Classes of Lipoproteins & Their Fates. 2  I. Dietary Sources of Lipids * Animal sources (mainly as fats): ✓ e.g. Dairy products like milk, butter, ghee, meat, fish, etc. * Vegetable sources (mainly as oils): ✓ e.g. Various cooking oils from various seeds namely sunflower oil, groundnut oil, cottonseed oil, mustard oil, etc. 3 II. Types of Dietary Lipids Undergoing Digestion ❑ Different forms of Dietary Lipids are driven to digestion & then absorption processes including 1.Neutral fats or Oils (Triacylglycerol; TAGs). 2. Phospholipids (PLs). 3. Cholesterol Esters (CEs; fatty acid + cholesterol). 4. Free Fatty acids (F.F.As) and Glycerol. **Important Note: ✓ Free Fatty acids and glycerol do not require any digestion because they are absorbed as such. 4  III. Digestion of Lipids Journey From Mouth to Intestinal juice… * Stage I: Digestion of Lipids in Mouth * Lingual lipase ✓ Secreted by dorsal surface of Tongue. ✓ But, this enzyme is Not significant in Adult humans. ✓ Little or No digestion of lipids occur in mouth. ✓ Action of Lingual lipase, if present (in Infants), starts in stomach as it is an acid-stable enzyme. 5  III. Digestion of Lipids * Stage II: Digestion of Lipids in Stomach * Gastric lipase ✓ Secreted by Stomach. ✓ Lipids requires Slightly Acidic pH (pH 6) for digestion. ✓ This lipase hydrolyzes TAG molecules, particularly those are found in Milk fat. Consequently, it particularly plays an important role in lipid digestion in Infants for whom Milk fat is the Primary source of Calories. ** Note: Stomach pH in Adults is (1.5-2.5), While, it is (4-6) in Infants. 6  III. Digestion of Lipids ** Stage III: In the Small Intestine Acidic Chyme containing dietary fat passes from stomach to duodenum, that inturn stimulate the secretion of pancreatic juice. Generally, Digestion of lipids in Upper Small Intestine (duodenum) proceeds by 2 main steps I. Emulsification II. Hydrolysis Bile salts acts as an Pancreatic juice contains a effective emulsifying agent number of lipolytic enzymes (lipases) of different lipids. 7 for fats.  III. Digestion of Lipids Follow… ** Stage III: In the Small Intestine I. Emulsification Bile Salt Role of Bile Salts in Lipid Digestion Bile salts are required for proper functioning of pancreatic lipase enzyme 1. Bile salts help in combination of lipase with co–lipase (small protein) in the intestinal lumen. 2. Bile salts help in the emulsification of fats as follows. As water–soluble lipases can act only on the surface of water–insoluble fat droplets so, bile salts help in lipase activity by emulsifying fats into fine droplets by lowering the surface tension and thus increasing the surface area 8 of these droplets for pancreatic lipase activity.  III. Digestion of Lipids Follow… ** Stage III: In the Small Intestine II. Hydrolysis ✓ Action of Pancreatic enzymes (Pancreatic juice) on Dietary lipids in Small intestine Pancreatic lipase TAGs 2-Monoacylglycerol (MAG) + 2 F.F.As. Phospholipase A2 Phospholipids Lysophospholipids Cholesterolesterase Cholesterol Ester Cholesterol + F.F.A 9  III. Digestion of Lipids (Turning from Digestion to Absoption) 1. Primary Link.. Products of Fat Digestion 2. Bile Salts/Acids Aid in Micelle Formation 3.Absorption of Micelles 10  IV. Absorption of Lipids (Formation of Chylomicrons) “Mechanism of Lipid Absorption” (3 Stages) 1. Passive Diffusion of Micelles * Micelles reaches bruch border of intestinal mucosal cells. * Lipid compounds from micelles pass passively through mucosal cells and are absorbed. 2. Re-Estrification & Assembly of Chylomicron 3. Exocytosis to Lymph then to Blood 11  IV. Absorption of Lipids Main Stage: Re-estrification & Assembly of Chylomicrons ✓ Resynthesis of triglycerides now occurs, by the utilization of partial glycerides and the liberated free acids. ✓ The resynthesized triglycerides then pass into the lymphatics of the abdominal cavity and through the thoracic duct the fats appear in blood as Lipoprotein particles called Chylomicrons. ✓ Structurally the Chylomicrons consist mainly of: A Triglyceride Core covered with Phospholipids and Protein Outer Layer. 12  Schematic Representation: Summery of Digestion & Absorption of Lipids BIOC 302 – Vitamins and Inorganic Metabolism Lecture 13 1: Homeostasis  V.Clinical Significance: Defect in Digestion & Absorption of Lipids “Steatorrhea” (Lipid Malabsorption) ✓ A clinical condition manifested by increased fat content of faeces (daily excretion of fat in faeces exceeds 6 gm/day). ✓ Causes Defective digestion & absorption of fat. 14  VI. Lipids Transport : Lipoproteins Definition, Importance & Structure of Lipoproteins ✓ Definition: Lipoproteins are large water soluble spherical complexes. ✓ Importance: Lipoproteins transport lipids from various tissues for storage & utilization. ✓ Lipoproteins Structure: - hydrophobic Core- TAGs & Cholesterol Esters. - hydrophilic Surface- Phospholipids, Unesterified cholesterol & Apoproteins. 15  VI. Lipids Transport : Lipoproteins Exogenous & Endogenous Pathways of Lipid Transport ✓ All lipids in plasma are transported in HDL the form of lipoproteins. Transport process is generally divided into 2 stages (pathways) A. Exogenous B. Endogenous Pathway Pathway Transport Transport lipids dietary lipids from Liver to from intestine to peripheral tissues. Liver. VLDL (Very Low Density Chylomicrons 16 Lipoproteins)  VI. Lipids Transport : Lipoproteins Transport Function of Lipoproteins & Their Fates Lipoprotein Source Transported lipids Fate Chylomicrons (CM) Small Transport Dietary Chylomicron remnants containing Intestine Exogenous TAG from the cholesterol and remaining fat are intestine to adipose tissue. removed from the blood by the liver. Very Low Density Liver Transport Endogenously Lipoprotein (VLDL) synthesized TAG in liver to Circulate deposited fats in all peripheral tissues e.g. tissues and become LDL. adipose tissue for storage. Low Density Derived from Transport of Cholesterol Eventually removed from the blood Lipoprotein (LDL: VLDL in synthesized in the liver to by the liver and other tissues in a Bad Cholesterol) circulation peripheral tissues. lesser degree. High Density Liver Transport of Excess tissue Eventually removed from the blood Lipoprotein (HDL: Cholesterol to liver for primarily by the liver. Good Cholesterol) disposal in feces. 17 VI. Lipids Transport : Lipoproteins Clinical Significance Elevated levels of cholesterol in the body can be associated with some pathogenic conditions as; a) Heart Diseases. b) Atherosclerosis. c) Gallstones. 18  VII.Lipid profile ✓ Lipid profile is a blood test looks at the levels of cholesterol and other fats as TAG in blood. ✓ You might need this test if your doctor wants to assess your risk of heart disease and stroke. ✓ You will usually need to fast for 8 to 12 hours before having this test. A lipid profile measures the following fats: Total cholesterol, LDL ("bad") cholesterol, and HDL ("good") cholesterol. TAG. The atherogenic index of plasma (AIP) that may be an important predictor of atherosclerosis and cardiovascular disease; if its value exceeds 1. Atherogenic index can be calculated from the following formulas: 1. Atherogenic index = LDL-cholesterol / HDL-cholesterol 2. Atherogenic index = TAG concentration / HDL-cholesterol 19 THE END