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lipid digestion MD(1).pptx

  1. Part-One Chemistry of lipids  Digestion, Absorption,  Secretion And Utilization
  2. Objectives Define lipid and its classification  what is essential fatty acids , give an example  Define cholesterol and is structure  describe the biological importance of cholesterol  Clinical importance “atherosclerosis “ Describe how fat is digested and absorbed  What is Emulsification Describe maldigestion and mal absorption of fat  list GIT hormones and there role in fat digestion
  3. Reference Books  Marks´ Basic Medical Biochemistry A Clinical Approach, third edition, 2009 (M. Lieberman, A.D. Marks)  Champe, P.C., Harvey, R.A. and Ferrier, D.R., Lippincott’s Illustrated Reviews: Biochemistry, 4th or 5th Edition, Lippincott Williams & Wilkins, Baltimore, MD 2008 or 2011.
  4. Biomedical Importance The lipids are a heterogeneous group of compounds, including fats, oils, steroids, waxes.  They have the common property of being: Relatively insoluble in water and Soluble in non-polar solvents such as ether &chloroform.
  5. Importance :  They are important dietary constituents because of: a. Their high energy value b. The fat-soluble vitamins and the essential fatty acids contained in the fat of natural foods  Fat is stored in adipose tissue, as a thermal insulator in the subcutaneous tissues and around certain organs  Non-polar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves.
  6.  Combinations of lipid and protein (lipoprotéines) serving also as the means of Transporting lipids in the blood  Knowledge of lipid biochemistry is necessary in understanding many important biomedical areas such as Obesity, diabetes mellitus, Atherosclerosis, and the role of various polyunsaturated fatty acids in nutrition and health.
  7.  Simple Lipids  Complex Lipids:
  8.  Simple lipids: Esters of fatty acids with various alcohols. Fats: Esters of fatty acids with glycerol. Oils and Waxes are a good example  Complex lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid. Example : Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue.
  9.  Glycolipids : Lipids containing a fatty acid, sphingosine, and carbohydrate.  Other complex lipids: Lipids such as sulfolipids and aminolipids. Lipoproteins may also be placed in this category.
  10. Fatty Acids  Fatty acids are building block of most lipids,  Having one polar carboxyl group (head) and a non-polar hydrocarbon chain (tail).  Fatty acids occur mainly as esters in natural fats and oils but do occur in the unesterified form as free fatty acids, a transport form found in the plasma.
  11.  Fatty acids that occur in natural fats has even number of carbon atoms.  The chain may be saturated (no double bonds) or unsaturated ( one or more double bonds).
  12.  Thus, Saturated acids end in -anoic, e.g. octanoic acid, and Unsaturated acids with double bonds end in -enoic, e.g. octadecenoic acid (oleic acid).  Carbon atoms are numbered from the carboxyl carbon (carbon No. 1). the terminal methyl carbon is known as the ω or n-carbon.
  13.  Various conventions use Δ for indicating the number and position of the double bonds . e.g. Δ9 indicates a double bond between carbons 9 and 10 of the fatty acid;  ω9 indicates a double bond on the ninth carbon counting from the ω- carbon.  In animals, additional double bonds are introduced only between the existing double bond (E.g., ω9, ω6, or ω3)
  14. Unsaturated Fatty Acids Contain One or More Double Bonds Fatty acids may be further subdivided as follows:  Monounsaturated containing one double bond.  Polyunsaturated containing two or more double bonds.  Eicosanoid: (20-Carbon) polyenoic fatty acids, comprise  the Prostanoids, leukotrienes (LTs), lipoxins (LXs).  Prostanoids include prostaglandins (PGs), prostacyclins  (PGIs), and thromboxanes (TXs).
  15. Some Common Examples
  16.  Most Naturally Occurring Have cis Double Bonds.  If on the same side of the bond, it is cis-, as in oleic acid  if on opposite sides, it is trans-, as in “Elaidic acid,” Geometric isomerismof Δ9, 18:1 fatty acids (oleic and Elaidic acids).
  17. TRIACYLGLYCEROLS (TRIGLYCERIDES)* ===Are the main storage forms of fatty acids  The triacylglycerols are esters of glycerol &fatty acids.  Mono- and diacylglycerol wherein one or two fatty acids are esterified with glycerol are also found in the tissues.
  18.  Enzymes readily distinguish between them and are nearly always specific for one or the other carbon;  E.g. Glycerol is always phosphorylated on sn-3 by Glycerol kinase to give glycerol 3-phosphate and not glycerol-1-phosphate . This glycerol kinase enzyme is specifically present only in liver
  19.  All of the steroids have a similar cyclic nucleus resembling phenanthrene (rings A, B, and C) to which a cyclopentane ring (D) is attached.  The carbon positions on the steroid nucleus are numbered as shown in Figure What is Cholesterol
  20. Cholesterol Is a Significant Constituent of Many Tissues  Cholesterol is widely distributed in all cells of the body but  particularly in nervous tissue.  It is a major constituent of the plasma membrane and  major constituent of plasma lipoproteins.  It is often found as cholesteryl ester, wherethehydroxyl groupon position 3 is esterified with a long-chain fatty acid.  It occurs in animals but not in plants. HO
  21. What are the physiologically important roles of cholesterol ??
  22. Steroids Play Many Physiologically Important Roles Biochemically it is also of significance because it is the precursor of a large number of equally important steroids that include Bile acids, Adrenocorticalhormones, Sex hormones, D vitamins, cardiac glycosides, and some alkaloids.
  23.  For the synthesis of Bile Salts that are important in lipid digestion and absorption.  For the synthesis of Steroid Hormones that are biologically important like the sex hormones estrogen and progesterone.  For the synthesis of vitamin D3  As a structural material in Biological Membranes.  As a component of Lipoproteins as transport of lipid Cholesterol is important in many ways:
  24. Metabolism of dietary lipids Digestion, and Absorption
  25. In infants :  Digestion begins in stomach catalyzed by the acid- stable lingual lipase from glands at the back of the tongue.  It digests short or medium chain fatty acids such as those found in milk fat  However, the rate of hydrolysis is slow because the lipid is not yet emulsified. 1st Processing In Stomach
  26.  These TAG molecules can be degraded by a separate gastric acid lipase. This enzyme is active only at neutral PH Therefore, of little use in the adult stomach where, the ph is low, but is active In neonates whose stomach PH is nearer to neutrality and whose diets contain mainly milk lipids.  Overall in adults dietary lipids are not digested to any extent in the mouth or the stomach but rather progress more or less intact to the small intestine.
  27. 2nd Emulsification in the small intestine  Emulsification of dietary lipids in the small intestine (duodenum)  Emulsification increases the surface area of the hydrophobic lipid droplets so that the digestive act effectively.  Emulsification is accomplished by two mechanisms namely:  The use of the detergent ( amphipathic ) surface active properties of bile salts synthesized in the liver and stored in the gall bladder and
  28. First step in processing dietary fats is emulsification.  Emulsification breaks lipid droplets into smaller-sized structures, which increases their overall surface area.  This process involves mixing (peristalsis) in the duodenum with bile salts, act like detergents to dissolve lipid droplets. The increased contact area between water and lipids facilitates interaction with digestive enzymes.
  29. By Several Pancreatic Lipases,  TAG hydrolyzed by Pancreatic Lipase at 1 and 3 C.  Into two types of product: free fatty acids (FFAs) and 2-monoacylglycerols.  The drug orlistat inhibits lipases and thereby prevents uptake of many fats as a means of treating obesity in conjunction with a low-calorie diet.  Phospholipids are hydrolyzed by phospholipases, which remove a fatty acid from carbon 2, and which may be further processed or absorbed. 3rd Degradation by pancreatic enzymes
  30. Overview of lipid digestion
  31. Hormonal Control of lipid digestion Cholecystokinin  site of release : from jejunum and lower duodenum In response to lipids and partially digested proteins entering small intestines.  Actions ; -Gall bladder-- contraction and release of bile - Pancreatic cells -- release of digestive enzymes - Decreases Gastricmotility
  32. Secretin  site –released from other intestinal cells - In response to low pH of chyme  Actions; - Release of a watery solution by pancreas and liver highin bicarbonate--appropriate pHfor action of pancreatic enzymes.
  33. Hormonal control of lipid digestion
  34. By micelles formation.  Mixed micelles = Bile salts, together with free fatty acids, free cholesterol and 2-monoacylglycerol form clusters of amphipathic lipids that coalesce with their hydrophobic groups inside and hydrophilic groups on the outside of the cluster, and which are soluble in the aqueous environment of the intestinal lumen. 4th Absorption of lipids by intestinal mucosal cells
  35. By micelles formation.  Short and medium chain-length fatty acids do not require the assistance of a micelle for absorption by the intestinal mucosa.
  36.  Mixed micelles are, therefore approach the primary site of lipid absorption, the brush border membrane (mucosal cell). Hydrophilic surface of the micelles facilitates the transport of the hydrophobic lipids to the brush border membrane where they are absorbed .
  37.  The mixture of lipids absorbed by the enterocytes migrates to the endoplasmic reticulum where biosynthesis of complex lipids takes place.  Fatty acids are first converted into their activated form by fatty acyl-CoA synthetase (thiokinase) .  Using the fatty Acyl CoA derivatives, the 2- monoacylglycerols absorbed by the enterocytes are converted to TAGs by the enzyme complex, TAG synthase. 5th Resynthesis of TAG and cholesteryl esters
  38.  Note: Virtually all long-chain fatty acids entering the enterocytes are used in this fashion to form TAGs, phospholipids, and cholesteryl esters.  Short- and medium-chain length fatty acids are not converted to their CoA derivatives Instead, they are released into the portal circulation,
  39.  Is the loss of > 6g of fat together with fat soluble vitamins (A,D,E,K) and essential fatty acids. 6th Lipid malabsorption (Steatorrhea):
  40. Causes of steatorrea:  Defective Digestion due to deficiency of pancreatic lipase as a result of chronic pancreatits,obstruction of pancreatic duct by tumors . Fecal fat is mostly undigested TAGs.
  41. Defective Absorption due to deficiency of bile salts as a result of bile duct obstruction as in tumors or stones of the bile duct. Fecal fat is in the form of 2-monoacylglycerol.  Also absorption may be due to defective intestinal mucosal cells (by surgical removal).
  42. Possible causes of steatorrea
  43.  Assembly of chylomicrons ( lipids are surrounded by a thin layer of Protein, Phospholipids And Unesterified Cholesterol.  This layer Stabilizes The Particle And Increases Its Solubility in aqueous solutions. 7th Secretion of lipids from intestinal mucosal cells.
  44.  Secretion Of Chylomicrons from intestinal mucosal cells into lymph (after a lipid- rich meal ( gives lymph a milky appearance = chyle, then chylomicrons are conveyed to the thoracic duct, then to the left subclavian vein, where they enter the blood).
  45.  Significance of Apolipoprotein B- 48 (the major Apolipoprotein in chylomicrons) ,synthesized in intestinal mucosal cells.  If not synthesized, chylomicrons will not be assembled and triacylglycerols accumulate in these cells leading to a genetic disorder, Congenital a-beta lipoproteinemia.
  46. Assembly & secretion of Chyle by Int. mucosal cells
  47. Use of dietary lipids by the tissues  TAGs in chylomicrons are broken primarily in the skeletal muscles and adipose tissue by LPL to glycerol and free fatty acids. LPL Triacylglycerols →→→… + 3 RcooH  Lipoprotein lipase is found on the luminal surface of endothelial cells of the capillary beds of the peripheral tissues.  Its deficiency in Familial lipoprotein lipase results in Massive Chylomicronemia.
  48.  Directly enter adjacent muscle cells or adipocytes.  Alternatively, free fatty acids may be transported by albumin ,until they are taken by cells.  Most cells can oxidize fatty acids to obtain energy.  However, the brain and other nervous tissues, erythrocytes and the adrenal medulla Can not  Adipocytes can also re-esterify free-fatty acids to produce triacylglycerols molecules, which are stored until the fatty acids are needed . Fate Of Free-fatty Acids
  49.  Glycerol to glycerol-3- phosphate by the liver for Glycolysis.  Fate of Chylomicron remnants are taken up by the liver where , they are hydrolyzed to their component parts due to Apolipoprotein E  Deficiency of Apolipoprotein E, leads to familial type III hyperlipoproteinemia which leads to Defective removal of Chylomicron -remnants from the plasma, Fate Of Glycerol
  50. Short answer Questions 1.Triacylglycerols are A. soluble in water B. partiallysoluble in water C. Insoluble in water D. None 2.What are the components of a triacylglycerols? 3.What are the sources of fattyacids? 4.At whichposition is the fattyacidattached to the cholesterol ring,? 5.which fatty acid should havethe least melting point out of the followings? Steric acid[0db] Arachidonic acid[4db], Timnodonic acid [5db] 6.Name a fatty acid with18 carbonatoms and a single double bond in trans configuration .7. Numbercarbons of cholesterol is -------------------
  51. Solution 1.Insoluble in water 2.Glycerol+3fattyacid 3.Diet, Endogenous synthesis and derivedfromadiposetissue by adipolysis. 4.3rd position 5.Timnodonicacid, since it has five double bonds; more the degree of unsaturation, lesser is the melting point. 6.Elaidic acid 7.27C