6. Dietary Lipids and Lipoproteins (1).pdf

MODULE 3 6 DIETARY LIPIDS AND LIPOPROTEINS 7 OBESITY 8 ATHEROSCLEROSIS 1  MODULE 3 6 DIETARY LIPIDS AND LIPOPROTEINS 7 OBESITY 8 ATHEROSCLEROSIS 2 6 DIETARY LIPIDS AND LIPOPROTEINS...

MODULE 3 6 DIETARY LIPIDS AND LIPOPROTEINS 7 OBESITY 8 ATHEROSCLEROSIS 1  MODULE 3 6 DIETARY LIPIDS AND LIPOPROTEINS 7 OBESITY 8 ATHEROSCLEROSIS 2 6 DIETARY LIPIDS AND LIPOPROTEINS 3  4. DIETARY LIPIDS AND LIPOPROTEINS — CONTENTS — I. DISTRIBUTION OF DIETARY LIPIDS IN HUMANS Stages of absorption and distribution of lipids From capillaries to tissues II. TRANSPORT OF CHOLESTEROL AND TRIACYLGLYCEROLS Lipoprotein structure Apolipoproteins Chylomicron - Chylomicron remnant VLDL VLDL - LDL LDL HDL LDL, HDL, and liver receptors III. GUIDELINES FOR CHOLESTEROL AND TRIGLYCERIDES 4  4. DIETARY LIPIDS AND LIPOPROTEINS – LEARNING OBJECTIVES – Discuss how dietary lipids contribute to the formation of lipoproteins synthesized by liver Remember the individual steps of absorption and distribution of dietary lipids in humans Discuss the transport of cholesterol to different tissues and assign a role to the different plasma lipoproteins. Recognize what type of apoprotein interacts with the tissue-specific receptors for lipoproteins Outline the function of Apoproteins Remember the guidelines for cholesterol and triglycerides 5 I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS 6 I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS Stages of absorption and tissue distribution of lipids The processing of dietary lipids in humans can be viewed in eight steps: fats ingested triacylglycerols triglycerols fats ingested in the in diet the diet cholesterol cholesterol 8 fatty fatty acids acidsare areoxidized oxidized as as fuel fuel or oresterified esterifiedfor for storage storage gallbladder gallbladder adipocyte small small intestine intestine fatty acids 7 fatty acidsenter entercells cells bile salts 1 bile salts emulsify emulsify Lipoprotein lipoprotein lipase in the capillary, is lipase dietary fats dietary fatsin inthe the 66lipoprotein activated lipase, by ApoC-II activatedand converts small intestine, intestine,forming forming bytriacylglycerols to fatty acids and ApoC-II in the capillary mixed micelles mixed micelles glyceroltriacylglycerols to converts capillary fatty acids and glycerol intestinal lipases 2 intestinal lipases intestinal degrade triacylglycerols mucosa 5 chylomicronsmove chylomicrons move degrade triacylglycerols through throughthethelymphatic lymphatic systemto system totissues tissues chylomicron fatty acids 3 fatty acidsare aretaken takenup up by 4 triacylglycerols triacylglycerolsare areincorporated incorporated by the the intestinal intestinal mucosaand mucosa and with with cholesterol cholesteroland andapoproteins apoproteins converted into converted intotriacylglycerols triacylglycerols into into chylomicrons chylomicrons Lehninger, 2nd Edition 7  I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS Stages of absorption and tissue distribution of lipids 1 Dietary lipids (mainly, triacylglycerols (TG) and cholesterol (C) are absorbed through the intestinal wall and are converted into dispersed micelles by bile salts. 2 Water-soluble lipases (mainly pan- LUMEN GUT INTESTINAL MUCOSAL creatic lipase) catalyze the formation triglycerides CELLS cholesterol of monoacylglycerols (MG), diacyl-  bile salts chylomicron glycerols (DG), free fatty acids (emulsification) (FFA), and glycerol in gut. apoproteins  B48 CII TG 3 The products of lipase action diffuse TG C C to the intestinal mucosal cells and C they are converted back into triacyl-  pancreatic lipase TG glycerols.  4 Triacylglycerols are packed together FFA glycerol FFA DG MG with dietary cholesterol and apopro- glycerol MG teins (B48, ApoC-II) to form lipopro- tein aggregates known as chylomicrons. 8  I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS Stages of absorption and tissue distribution of lipids 5 Chylomicrons are transferred to different tissues through the lymphatic system 6 Lipoprotein lipase in the capillaries –activated by the apoprotein Apo C-II– catalyzes the release of fatty acids and LYMPHATIC CAPILLARIES VESSELS glycerol CO2 H2O 7 Most of these fatty acids and chylomicron chylomicron energy glycerol are incorporated into lipoprotein   lipase adipocytes and stored as lipid fatty fatty  acids acids droplets fatty acids chylomicronremnant 8 or are metabolized for the  formation of energy (ATP) in TG muscle. glycerol-P glucose 9  I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS STEPS 1-4 STEPS 5-8 LUMEN GUT INTESTINAL LYMPHATIC CAPILLARIES MUCOSAL VESSELS triglycerides CELLS cholesterol CO2 H2O bile salts chylomicron chylomicron chylomicron (emulsification) energy apoproteins lipoprotein B48 C-II lipase TG TG fatty fatty C C acids acids fatty acids C chylomicronremnant pancreatic lipase TG FFA TG glycerol FFA MG glycerol-P DG MG glycerol glucose 10  I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS STEPS 1-4 STEPS 5-8 LUMEN GUT INTESTINAL LYMPHATIC CAPILLARIES MUCOSAL VESSELS triglycerides CELLS cholesterol CO2 H2O bile salts chylomicron chylomicron chylomicron (emulsification) energy apoproteins lipoprotein B48 C-II lipase TG TG fatty fatty C C acids acids fatty acids C chylomicronremnant pancreatic lipase TG FFA TG glycerol FFA MG glycerol-P DG MG glycerol glucose 11  I. ABSORPTION AND DISTRIBUTION OF DIETARY LIPIDS IN HUMANS Stages of absorption and tissue distribution of lipids: From the capillaries to tissues Synergy between adipose tissue and muscle: when the blood levels of glucose are low, fatty acids from adipocytes are mobilized to myocytes (as conjugates with albumin). The degradation of adipocyte triacylglycerols is regulated by glucagon and epinephrine, two hormones that are released when the blood concentrations of glucose areepinephrine low. glucagon —glucagon receptor ATP AC ATP NADH cAMP glucose glycolysis PKA albumin TCA glycerol-P HSL acetyl-CoA β-oxidation acyl-CoA triacylglycerols fatty fatty acids acids adipocyte myocyte blood 12  II. TRANSPORT OF CHOLESTEROL AND TRIGLYCERIDES Plasma Lipoproteins Cholesterol, cholesteryl esters, triacylglycerols, and phospholipids (insoluble in water) are transported from the tissue of origin (absorption in intestine and synthesis in liver) by plasma lipoproteins, which are molecular aggregates of specific carrier proteins (apolipoproteins) with various combinations of cholesterol, cholesteryl esters, phospholipids, and triacylglycerols. There are four major classes of lipoproteins in human plasma: ________________________________________________________________________________________________________________ ________________________ Composition (%) _________________________ Lipoprotein density (g/ml) protein cholesterol cholesteryl phospho- Triacyl- esters lipids glycerols ________________________________________________________________________________________________________________ Chylomicrons