12.) Lipases: pancreatic, lipoprotein, hormone sensitive – their localization and roles, activating factors. Digestion and absorption of lipids in the GI tract.
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- FrontLipids and water solubilityBackLipids are hydrophobic and therefore cannot be digested and transported like water-soluble nutrients
- FrontOverall sequence of dietary lipid handlingBackEmulsification by bile salts, enzymatic digestion by pancreatic enzymes, absorption into enterocytes, re-esterification, packaging into chylomicrons, and transport through lymph then blood
- FrontThree major lipases in lipid metabolismBackPancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase
- FrontRole of pancreatic lipaseBackDigests dietary triacylglycerol in the intestine
- FrontRole of lipoprotein lipaseBackHydrolyzes triacylglycerol in chylomicrons and VLDL in capillaries
- FrontRole of hormone-sensitive lipaseBackMobilizes stored triacylglycerol in adipocytes
- FrontMajor dietary lipidsBackTriacylglycerols, cholesterol and cholesterol esters, phospholipids, and free fatty acids
- FrontMain dietary lipidBackTriacylglycerol
- FrontApproximate fraction of dietary lipid that is triacylglycerolBackUp to 90%
- FrontMain site of lipid digestionBackSmall intestine
- FrontKey helpers in intestinal lipid digestionBackBile salts, pancreatic lipase, colipase, and pancreatic bicarbonate
- FrontHormone that stimulates release of bile and pancreatic enzymesBackCholecystokinin (CCK)
- FrontHormone that stimulates bicarbonate secretionBackSecretin
- FrontWhere lipid digestion products go before absorptionBackThrough the unstirred water layer to the enterocyte surface
- FrontWhy bile salts are needed in lipid digestionBackLipids are insoluble in water and must be emulsified
- FrontMeaning of emulsification in lipid digestionBackDispersing immiscible liquids into an emulsion
- FrontRole of bile salts in lipid digestionBackBreak large fat droplets into smaller droplets to increase surface area for lipase action
- FrontAdditional role of bile salts in lipid absorptionBackHelp form mixed micelles that deliver lipid digestion products to the enterocyte surface
- FrontHigh-yield fact about bile saltsBackBile salts do not hydrolyze fat; they emulsify it and help absorption
- FrontSite of secretion of pancreatic lipaseBackPancreas
- FrontSite of action of pancreatic lipaseBackIntestinal lumen of the small intestine
- FrontRole of pancreatic lipase in intestinal digestionBackDigests dietary triacylglycerol
- FrontStepwise products of pancreatic lipase action on TAGBackDiacylglycerol, then 2-monoacylglycerol and free fatty acids
- FrontHigh-yield final products of pancreatic lipase digestionBack2-monoacylglycerol and free fatty acids
- FrontKey helper for pancreatic lipaseBackColipase
- FrontWhy colipase is needed for pancreatic lipaseBackBile salts coat lipid droplets and can interfere with lipase binding, so colipase helps lipase bind at the lipid-water interface
- FrontRole of bicarbonate in pancreatic lipase functionBackNeutralizes acidic chyme and provides a better pH for pancreatic enzymes
- FrontHormonal support for pancreatic lipase actionBackCCK promotes delivery of pancreatic enzymes and bile, and secretin promotes bicarbonate secretion
- FrontHigh-yield distinction for pancreatic lipase activationBackPancreatic lipase works with colipase, not apo CII, and is not activated by phosphorylation
- FrontMajor absorbable products of intestinal lipid digestionBackFree fatty acids, 2-monoacylglycerols, cholesterol-related lipids, and other lipid products in micelles
- FrontVehicle that carries lipid digestion products to the microvilliBackMixed micelles
- FrontPath lipid digestion products take to enterocytesBackThey move through the unstirred water layer to the luminal surface of enterocytes
- FrontHow long-chain fatty acids and monoacylglycerols enter enterocytesBackMainly by passive diffusion
- FrontTransporters that help long-chain fatty acid uptakeBackFATP transporters
- FrontWhen FATP is especially helpfulBackAt low luminal long-chain fatty acid concentration
- FrontIntracellular binding protein for long-chain fatty acids in enterocytesBackFABP
- FrontDestination of long-chain fatty acids inside enterocytesBackSmooth endoplasmic reticulum
- FrontAbsorption of short-chain and medium-chain fatty acidsBackAbsorbed directly into intestinal cells without bile salts
- FrontTransport route of short-chain and medium-chain fatty acidsBackPortal vein to the liver
- FrontHandling of long-chain fatty acids after absorptionBackThey are re-esterified in enterocytes and leave in chylomicrons
- FrontHigh-yield absorption distinctionBackSCFA and MCFA go to portal blood, whereas LCFA go to chylomicrons and lymph
- FrontWhat happens to FFA and MAG in enterocytesBackThey are recombined back to triacylglycerol in the smooth ER
- FrontWhat happens to triacylglycerol after re-esterification in enterocytesBackIt is packaged with other lipids and apoproteins into chylomicrons
- FrontRoute of chylomicron خروج from enterocytesBackInto the lymphatic system and then into the blood
- FrontHigh-yield summary of long-chain dietary fat handlingBackDigested, absorbed, re-esterified, and exported as chylomicrons
- FrontWhere chylomicrons first enter after leaving enterocytesBackLymphatic capillaries in the intestinal villi
- FrontPath of chylomicrons from lymph to bloodBackThrough lymph to the thoracic duct and then into the subclavian vein
- FrontMain job of chylomicronsBackTransport dietary triacylglycerols to peripheral tissues
- FrontLocalization of lipoprotein lipase (LPL)BackAttached to the luminal surface of endothelial cells in capillaries by proteoglycans or heparan sulfate
- FrontMajor tissues associated with LPLBackAdipose tissue, skeletal muscle, heart muscle, lactating mammary gland, lung, kidney, and liver
- FrontHigh-yield location fact for LPLBackLPL is not in the intestinal lumen or inside adipocyte cytosol; it acts on the capillary lumen side
- FrontRole of LPLBackHydrolyzes the triacylglycerol core of circulating lipoproteins
- FrontMain lipoprotein substrates for LPLBackChylomicrons and VLDL
- FrontProducts of LPL actionBackFree fatty acids and glycerol
- FrontFate of fatty acids released by LPL in adipose tissueBackStored as triacylglycerol
- FrontFate of fatty acids released by LPL in muscle and heartBackOxidized for energy
- FrontApproximate fraction of lipoprotein core TAG degraded by LPLBackAbout 90%
- FrontDirect activator of LPLBackApo CII
- FrontSource of apo CII for chylomicrons and VLDLBackHDL
- FrontEffect of insulin on LPLBackStimulates LPL synthesis and secretion to the capillary lumen, especially in adipose tissue
- FrontHigh-yield regulation summary for LPLBackLPL activator is apo CII, insulin increases it, and LPL acts on circulating TAG rather than stored adipocyte TAG
- FrontTissue difference in LPL according to lectureBackMuscle LPL has low Km and adipose LPL has high Km
- FrontFunctional implication of muscle versus adipose LPLBackMuscle uses fatty acids readily for oxidation, whereas adipose tissue stores them
- FrontLocalization of hormone-sensitive lipase (HSL)BackInside adipocytes at lipid droplets
- FrontHigh-yield location distinction between HSL and LPLBackHSL is inside adipose cells, whereas LPL is outside on capillary endothelium
- FrontRole of HSLBackMobilizes stored triacylglycerol during fasting or energy demand
- FrontProducts of adipose triacylglycerol hydrolysis by HSLBackFree fatty acids and glycerol
- FrontTransport form of fatty acids released from adipose tissueBackBound to albumin in the blood
- FrontHigh-yield HSL summaryBackHSL mobilizes stored fat and mediates lipolysis in adipose tissue
- FrontMechanism of HSL activationBackHormonal signaling through cAMP and protein kinase A (PKA)
- FrontClassic fasting hormones that activate HSLBackGlucagon and adrenaline or epinephrine
- FrontSequence of signaling that activates HSLBackHormone activates adenylate cyclase, cAMP rises, PKA activates lipolysis, and the HSL or perilipin system promotes access to stored TAG
- FrontEffect of insulin on HSL and lipolysisBackInsulin inhibits lipolysis and opposes HSL action
- FrontHigh-yield regulation summary for HSLBackHSL is activated by glucagon or epinephrine through cAMP and PKA and inhibited by insulin
- FrontComparison of pancreatic lipase, LPL, and HSLBackPancreatic lipase acts in the intestinal lumen on dietary TAG, LPL acts on capillary endothelium on TAG in chylomicrons and VLDL, and HSL acts inside adipocytes on stored TAG
- FrontLocation of pancreatic lipaseBackIntestinal lumen
- FrontSubstrate of pancreatic lipaseBackDietary triacylglycerol
- FrontProducts of pancreatic lipaseBack2-monoacylglycerol and free fatty acids
- FrontHelper for pancreatic lipaseBackColipase
- FrontIndirect helpers for pancreatic lipaseBackBile salts and a bicarbonate-supported intestinal environment
- FrontLocation of LPLBackLuminal surface of capillary endothelium
- FrontSubstrate of LPLBackTriacylglycerol in chylomicrons and VLDL
- FrontProducts of LPLBackFree fatty acids and glycerol
- FrontActivator of LPLBackApo CII
- FrontHormonal stimulation of LPLBackInsulin
- FrontLocation of HSLBackAdipocyte lipid droplets
- FrontSubstrate of HSLBackStored triacylglycerol
- FrontProducts of HSLBackFree fatty acids and glycerol
- FrontActivators of HSLBackGlucagon and epinephrine through cAMP and PKA
- FrontHormone that inhibits HSLBackInsulin
- FrontStep-by-step sequence of lipid digestion and absorptionBackDietary lipids enter small intestine, CCK stimulates gallbladder and pancreas, secretin stimulates bicarbonate, bile salts emulsify lipid droplets, pancreatic lipase and colipase digest TAG to 2-MG and FA, products form mixed micelles and cross the unstirred water layer to enterocytes, LCFA and MAG enter enterocytes while SCFA and MCFA go directly to portal blood, LCFA and MAG are re-esterified to TAG in smooth ER, TAG is packaged into chylomicrons, chylomicrons enter lymph then blood, and LPL hydrolyzes chylomicron TAG in capillaries
- FrontFraction of bile salts reabsorbed according to lectureBackAbout 95%
- FrontWhat happens to reabsorbed bile saltsBackThey circulate back to the liver
- FrontHigh-yield fact about bile salt recyclingBackBile salts are reused rather than lost after one meal
- FrontVery high-yield fact about pancreatic lipaseBackPancreatic lipase digests dietary TAG in the intestine
- FrontVery high-yield fact about colipaseBackColipase helps pancreatic lipase
- FrontVery high-yield fact about LPL locationBackLPL is on capillary endothelium, not inside cells
- FrontVery high-yield fact about LPL activationBackApo CII activates LPL
- FrontVery high-yield fact about insulin and LPLBackInsulin stimulates LPL in adipose tissue
- FrontVery high-yield fact about HSLBackHSL mobilizes stored adipose TAG
- FrontVery high-yield fact about HSL regulationBackGlucagon and epinephrine activate HSL, whereas insulin inhibits it
- FrontVery high-yield absorption distinction for fatty acidsBackLCFA leave the intestine in chylomicrons, whereas SCFA and MCFA go by portal vein
- FrontVery high-yield transport fact about chylomicronsBackChylomicrons enter lymph first and then blood
- FrontCheat-sheet pancreatic lipaseBackLocation is intestinal lumen, role is digestion of dietary TAG, products are 2-MG and free fatty acids, helper is colipase, and indirect helpers are bile salts and a bicarbonate-supported environment
- FrontCheat-sheet lipoprotein lipaseBackLocation is luminal surface of capillary endothelium, role is hydrolysis of TAG in chylomicrons and VLDL, products are fatty acids and glycerol, activator is apo CII, and insulin increases it
- FrontCheat-sheet hormone-sensitive lipaseBackLocation is adipocytes, role is mobilization of stored TAG, activators are glucagon and epinephrine through cAMP and PKA, and insulin inhibits it
- FrontCheat-sheet lipid digestion and absorptionBackBile salts emulsify, pancreatic lipase digests, micelles deliver products, LCFA are re-esterified in enterocytes, chylomicrons are formed, and transport proceeds from lymph to blood
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