Lipid Classification and Digestion PDF

 Lipids constitute a heterogeneous group of compounds of biochemical importance. Lipids may be defined as compounds which are relatively insoluble in water, but freely soluble in nonpolar organic solvents like benzene, chloroform, ether, hot alcohol, acetone, etc. Chemically they are v...

 Lipids constitute a heterogeneous group of compounds of biochemical importance. Lipids may be defined as compounds which are relatively insoluble in water, but freely soluble in nonpolar organic solvents like benzene, chloroform, ether, hot alcohol, acetone, etc. Chemically they are various types of esters of different alcohols. In addition to alcohol and fatty acids, some of the lipids may contain phosphoric acid, nitrogenous base and carbohydrates.  Bloor defined lipids as “naturally occurring compound which are insoluble in water, and soluble in one or more organic solvent such as benzene, chloroform, either acetone the so called fat solvent on hydrolysis field fatty acids which are utilized by the living organisms’’  CLASSIFICATION OF LIPIDS Bloor’s Classification is generally adopted with a few modifications as follows: I. Simple Lipids Esters of fatty acids with various alcohols: (a) Neutral fats (Triacylglycerol, TG): These are triesters 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. II. Compound Lipids Esters of fatty acids containing groups, other than, and in addition, to an alcohol and fatty acids. (a) Phospholipids: They are substituted fats containing in addition to fatty acid and glycerol, a phosphoric acid residue, a nitrogenous base and other substituents. Examples: phosphatidyl choline (Lecithin), phosphatidyl ethanolamine (Cephalin), phosphatidyl inositols (Lipositols), phosphatidyl serine, plasmalogens, sphingomyelins, etc. A. Glycerophospholipids B. Spingophospholipids ALCOHOL IS GLYCEROL ALCOHOL IS SPINGOSINE  Phosphatidylcholine  Phosphatidyl ethanolamine  Phosphatidyl serine  Spingomyelins  Phosphatidyl inositol  Plasmalogens  Cardiolipins (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. These are of two types: Cerebrosides Gangliosides (c) Sulpholipids: Lipids characterised by possessing sulphate groups. (d) Aminolipids (Proteolipids) (e) Lipoproteins: Lipids as prosthetic group to proteins. III. Derived Lipids 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 Straight chain alcohols are water insoluble alcohols of higher molecular weight obtained on hydrolysis of waxes. Cholesterol and other steroids including Vit D. Alcohols containing the β-ionone ring include Vit A and certain carotenoids. Glycerol.  DERIVED LIPIDS These are the derivatives obtained on the hydrolysis of group 1 and group 2 lipids which possess the characteristics of lipids. Example Cholestero Vitamin A Fatty acids Steroids l and D  Miscellaneous Aliphatic hydrocarbons include isooctadecane found in liver fat and certain hydrocarbons found in bees wax and plant waxes. Carotenoids Squalene is a hydrocarbon found in shark and mammalian liver and in human sebum. Vitamins E and K.  CLASSIFICATION (Functional) LIPIDS FUNCTIONS FATTY ACIDS Metabolic fuel; component of several other classes of lipids TRIGLYCERIDES Main storage form of fatty acids and chemical energy PHOSPHOLIPIDS Components of membranes; sources of arachidonic acid, inositol trisphosphate (IP3), and SPHINGOLIPIDS diglyceride (DAG) for Signal Transduction Components of membranes; Imp. in signal transduction  CLASSIFICATION (Functional) Contd Component of CHOLESTEROLmembranes; precursor of bile salts and steroid hormones BILE SALTS Lipid digestion and absorption; main product of  FUNCTIONS CONTD STEROID Intracellular signals that HORMONES regulate gene expression in target cells EICOSANOIDS Regulators of physiological Prostaglandins, /immunological functions. Thromboxanes, Local hormones Leukotrienes Vision; calcium VITAMINS metabolism; antioxidants; A,D,E,K blood coagulation CHOLINE  FATTY ACIDS Monocarboxylic Usually straight-chain having even number (2-26) of carbon atoms Most common are C12-C22 Short-Chain (2-4 C atoms) Medium- Chain (6-10 C atoms) Long-Chain (12-20 C atoms) Very long-Chain (C22 and above)  Saturated Fatty Acids Most Commonly occurring are Myristic Acid (14:0) Palmitic Acid (16:0) Stearic Acid (18:0) Since the carboxylic group is ionized at physiological pH, they exist as carboxylate ion e.g. palmitate CH3 (CH2)14-COOH CH3(CH2)14-COO- + H+ pKa 4.8  UNSATURATED FATTY ACIDS Contain carbon to carbon double bonds. MUFA Mono-unsaturated (1 double bond) OLEIC ACID 18:1 ( high concentrations in olive oil ) PUFA Polyunsaturated (> 1 double bond ) LINOLEIC ACID, 18:2 α-LINOLENIC ACID, 18:3  DIGESTION AND ABSORPTION OF LIPIDS The digestion of fats and other lipids poses a special problem because of (a) the insolubility of fats in water, and (b) because lipolytic enzymes, like of the enzymes, are soluble in an aqueous medium. Phases of Digestion and Absorption may be arbitrarily divided into three phases: Preparatory phase: Includes the digestion of lipids in the intestine. The large lipid particles are broken down into smaller particles with the help of lipolytic enzymes. Transport phase: Includes the transport of digested fats across the membrane of intestinal villous layer into intestinal epithelial cells. Transportation phase: Includes the events of action that take place inside intestinal epithelial cells and its passage through lacteals to lymph/or in portal blood.  Dietary Sources of Lipids The chief dietary sources of lipids in human beings: Animal source: Dairy products like milk, butter, ghee, etc. meat and fish, especially pork, eggs. Vegetable source: Various cooking oils from various seeds, viz. sunflower oil, groundnut oil, cotton seed oil, mustard oil, etc. and fats from other vegetable sources. However, unlike proteins, vegetable fats are superior to animal fats because: They contain more of polyunsaturated fatty acids Vegetable fats are less likely to go rancid due to presence of antioxidants. Digestion in mouth and stomach: little or no fat digestion takes place in the mouth. lipase has been detected called lingual lipase which is secreted by the dorsal surface of the tongue (Ebner’s gland). Lingual lipase: The pH of activity is 2.0 to 7.5 (optimal pH value is 4.0 to 4.5). Lingual lipase activity is continued in the stomach also where the pH value is low. Lingual lipase is more active on TG having shorter FA chains and is found to be more specific for ester linkage at 3-position milk fat appears to be the best substrate for this enzyme substrate for this enzyme. The released short chain fatty acids are relatively more soluble and hydrophilic Gastric lipase: There is evidence of presence of small amounts of gastric lipase in gastric secretion.  No emulsification of fats takes place in stomach The enzyme secreted in small quantity pH of gastric juice is not conducive which is highly acidic, whereas gastric lipase activity is more effective at relatively alkaline pH (average pH 7.8). Gastric lipase activity requires presence of Ca.++ Role of fat in stomach: Fats do play one important role in the stomach in that they delay the rate of emptying of stomach, presumably by way of the hormone enterogastrone, which inhibits gastric motility and retards the discharge of bolus of food from the stomach. Thus fats have a high satiety value.  Digestion in small intestine: The major site of fat digestion is the small intestine. This is due to the presence of a powerful lipase (steapsin) in the pancreatic juice and presence of bile salts, which acts as an effective emulsifying agent for fats Pancreatic juice and bile enter the upper small intestine, the duodenum, by way of the pancreatic and bile ducts respectively. Secretion of pancreatic juice is stimulated by the: Passage of an acid gastric contents (acid chyme) into the duodenum By secretion of the GI hormones, secretin and CCKPZ.  Secretin: Increases the secretion of electrolytes and fluid components of pancreatic juice. Pancreozymin of CCK-PZ: Stimulates the secretion of the pancreatic enzymes. Cholecystokinin of CCK-PZ: Causes contraction of the gallbladder and discharge the bile into the duodenum. Discharge of bile is also stimulated by secretin and bile salts themselves. Hepatocrinin: Released by the intestinal mucosa stimulates more bile formation which is relatively poor in the bile salt content. Pancreatic juice has been shown to contain a number of lipolytic enzymes: 1. Pancreatic lipase (steapsin) 2. Phospholipase A (Lecithinase) 2 3. Cholesterol esterase Pancreatic lipase (steapsin): It is an esterase with optimum pH value of 6. Role of bile salts in pancreatic lipase activity: Bile salts are required for proper functioning of the enzyme. Enhances the lipase activity of the intestinal pH. Also protects the enzyme against inhibitory effects  (b) Bile salts also help in emulsification of fats. Role of Ca++: In the presence of Ca++ in the intestine, the FFA are immediately precipitated as ‘soaps’ (insoluble Ca-soaps) and are thereby prevented from inhibiting further lipase action. Thus, Ca++ facilitates lipase action. The overall digestion of fats, brought about by gastric lipase is negligible because: No emulsification of fats takes place in stomach The enzyme secreted in small quantity pH of gastric juice is not conducive which is highly acidic. Gastric lipase activity requires presence of Ca++. Role of fat in stomach: Fats do play one important role in the stomach they delay the rate of emptying of stomach, presumably by way of the hormone enterogastrone, which inhibits gastric motility and retards the discharge of bolus of food from the stomach. Thus fats have a high satiety value.  1. Role of bile salts in pancreatic lipase activity: Bile salts are required for proper functioning of the enzyme. (a) Bile salts help in combination of ‘lipase’ with two molecules of a small protein called as colipase (mol wt = 10,000) in the intestinal lumen. This combination of lipase with colipase has two effects: Enhances the lipase activity of the intestinal pH. Also protects the enzyme against inhibitory effects of bile salts and against surface denaturation. (b) Bile salts also help in emulsification of fats.  Mode of action of pancreatic lipase: The complete hydrolysis of fats (TG) produces glycerol and FA.  The complete hydrolysis of fats (TG) produces glycerol and FA. Pancreatic lipase is virtually specific for the hydrolysis of “primary ester linkage”. It cannot readily hydrolyse the ester linkage of position-2 (β), if it does so it occurs at a very slow rate. Digestion of TG molcule by pancreatic lipase proceeds First by removal of a terminal FA to produce an α, β-diglyceride The other terminal FA is then removed to produce a β- monoglyceride.  “Micelle” formation: Bile salts and soaps formed in the intestinal lumen and bicarbonates of pancreatic and intestinal juices, collect the molecules of higher FA, mono and diglycerides, lecithins, cholesterol, etc. in the form of “water-soluble molecular aggregates” called mixed “micelles”  B. TRANSPORT PHASE FFA, and monoglycerides mainly enter the microvilli and the apical pole of absorptive epithelial cells by “simple diffusion” through the cell-membrane. Short and medium chain FA (6 to 10 C) and unsaturated FA are more readily absorbed than the ling-chain FA (12 to 18 C). by “simple diffusion” through the cell-membrane. taken up by the smooth endoplasmic reticulum and resynthesised into TG again by enzymes present in the membrane and/or cavities of the reticulum. TG resynthesis are formed as well as the protein component (apo- B48) of lipoprotein complex, chylomicron.  C. TRANSPORTATION PHASE Intestinal lipase: A lipase distinct from that of the pancreatic lipase is present in the intestinal mucosal cell. Principal action of this enzyme is confined within the epithelial cell. FA absorbed from intestinal lumen and FA formed from hydrolysis of α-monoglycerides, are activated to “Acyl-CoA”. An ATP- dependant thiokinase has been shown to be present in the mucosal cells of the intestine. Glycerol is converted to α-Glycerol-(P) by glycerokinase in presence of ATP.  ABSORPTION OF LIPIDS 1. Glycerol Free glycerol (22%) released in the intestinal lumen is not utilised for resynthesis of TG in intestinal epithelial cell. It directly passes to the portal vein and taken to liver. 2. Fatty Acids (FA) Short-chain FA and medium-chain FA (less than 8 to 10 C) and unsaturated FA are absorbed to portal blood directly and taken to Liver. all FFA present in the intestinal wall are ultimately reincorporated in TG “esterified FA” in the lymph of the lacteals, which passes through thoracic duct to systemic circulation.  ABSORPTION OF LIPIDS Fate of resynthesised TG: Re-esterification to form TG molecule takes place in the cisternae of endoplasmic reticulum of the mucosal cells it is converted to lipoprotein complex called chylomicrons Chylomicrons: synthesised in the intestinal wall. Size of chylomicrons range from 0.075 to 1 m. It is composed largely of TG, cholesterol TG: 87 to 88 per cent PL: Approximately 8 per cent Free and esterified cholesterol: Approximately 3 per cent and Specific “apo-β48” protein: 0.05 to 2 per cent.  ABSORPTION OF LIPIDS Chylomicrons pass out through the cell membrane of bases and lateral walls of intestinal epithelial cells And moves through extracellular spaces between those cells to enter lymphatic vessels of abdominal region and later goes to systemic circulation through the thoracic duct.  Functions of Lipids 1. Storage form of energy (triglycerides) 2. Structural components of biomembranes (phospholipids and cholesterol) 3. Metabolic regulators (steroid hormones and prostaglandins) 4. Act as surfactants, detergents and emulsifying agents (amphipathic lipids) 5. Act as electric insulators in neurons 6. Provide insulation against changes in external temperature (subcutaneous fat) 7. Give shape and contour to the body 8. Protect internal organs by providing a cushioning effect (pads of fat) 9. Help in absorption of fat soluble vitamins (A, D, E and K) 10. Improve taste and palatability of food.