Unformatted text preview:

Section VI. Lipid MetabolismOverview Fatty acid metabolismOverview of cholesterol metabolismOverview lipoprotein particles in bloodLipid metabolism overviewChapt. 32I. Digestion of dietary triacylglycerolsDigestion, absorptionEnzymes degrade lipidsAbsorptionIII. ChylomicronsBlood lipoproteinsTransport of lipids in bloodNascent ChylomicronsApoprotein B geneIV. Lipoprotein particles transport dietary lipids in bloodFate of chylomicronsOlestraKey concepts:Review questionSection VI. Lipid MetabolismSection VI. Lipid metabolism overview:Major categories of lipids (not very water-soluble):•Fatty acids and triagylclycerol (TG)•Glycerophospholipids and sphingolipids•Eicosanoids (prostaglandins, thromboxanes)•Cholesterol, bile salts, steroid hormones•Fat-soluble vitamins (A, D, E, K)TriacylglycerolOverview Fatty acid metabolismFatty acid metabolism: (Chapts. 32, 33)•Fatty acids can be dietary or synthesized in liver•Can be oxidized for energy → CO2 and H2O•Can be stored as triacylglycerol in adipose tissue• Can be used to make phospholipids and sphingolipids for membrane componentsOverview of cholesterol metabolismCholesterol metabolism (chapt. 34):•Is incorporated into membranes for stability•Is a precursor for bile salts (gall bladder secretes)•Is a precursor for steroid hormonesOverview lipoprotein particles in bloodLipoprotein particles transport lipids in blood:Triacylglycerol is major dietary lipid:•Digested in intestinal lumen: free FA and 2-mono-acylglycerol are reconverted to TG in intestinal cells•TG are packaged as chylomicrons (apoB) and secreted into blood ; matured with additional proteins•VLDL (very-low-density-lipoproteins) produced in liver from dietary carbohydrates (insulin stimulated)•Lipoprotein lipase (LPL) on cells degrades the lipoproteins; FA into cells• HDL (high-density-lipoproteins) transport excess cholesterol to liver; exchange proteinsLipid metabolism overviewTriacylglycerol metabolism:Fed state:•TG digested to 2-MG and FA, into intestinal cells•TG reform (chylomicrons) with protein, into blood•Liver forms VLDL by lipogenesis from sugars•VLDL donates protein to chylomicron, which binds LPL on cells and is cleaved to release FA into muscle, adiposeFasting state:•Fatty acids, glycerol released from adipose•Glycerol used for gluconeogenesis liver•FA used for ketone bodies, or oxidation (muscles, other)Chapt. 32Ch. 32 Digestion and Transport of Dietary LipidsStudent Learning Outcomes:• Explain digestion of triacylglycerols (TG) to free fatty acids (FA) and 2-monoacylglycerol (2-MG)• Describe the role of bile salts in this process• Describe how micelles enter epithelial cells, and are reconverted to TG • Explain how TG plus apoproteins and other lipids form nascent chylomicrons that exit cells• Describe role of HDL lipoproteins to mature the nascent chylomicrons, and breakdown of particlesI. Digestion of dietary triacylglycerolsI. Digestion of dietary triacylglycerols•Major fat in diet (storage of lipids plants, animals)•Lipases digest to 2-monoacylglycerol (2-MG)•Bile salts emulsify fat in small intestine•Bile salts derived from cholesterolFig. 1 fatty acids in triacylglycerolFig. 2, a bile saltDigestion, absorptionFig. 3:TG, triacylglycerol;BS, bile salt, FA, fatty acid2-MG, 2-monoacylglycerolDigestion of dietary triacylglycerols:•Lipases digest•Bile salts emulsify, colipases aid lipases•TG reform in epitheliumEnzymes degrade lipidsEnzymes degrade lipids:•Lipases cleave C1, C3 of TG•Cholesterol esterase removes FA•Phospholipase degrades phospholipidFigs. 5,6AbsorptionFigs. 3,6Absorption into intestinal epithelial cells:• FA, 2-MG, cholesterol, other lipids, BS in micelles • Lipids absorbed through microvilli, not bile salts• Bile salts are recycled• Short, med-chain FA absorb directly epithelium, enter bloodstream bound to serum albuminIII. ChylomicronsIII. Chylomicrons•TG are resynthesized in intestinal epithelia•ATP activates FA → FA-CoA (in Smooth ER)• Apoproteins and other lipids bind[synthesis of TG in liver, adipose starts with phosphatidic acid]Fig. 7Blood lipoproteinsBlood lipoprotein particles transport lipids:•Chylomicrons – produced in intestinal cells from dietary fat; carry TG in blood•VLDL – produced from liver mainly from dietary carbohydrate; carries TG in blood•IDL - produced in blood (remnant of VLDL)•LDL – produced in blood (remnant of IDL after TG digestion; high concentration of cholesterol; endocytosed by liver, other tissues (LDL receptor)•HDL – produced in liver, intestine; exchanges proteins and lipids with other lipoproteins; returns cholesterol to liverTransport of lipids in bloodTransport of lipids uses lipoprotein complexes:•Lipids are not soluble in water; would coalesce•Phospholipids, protein on outside; hydrophobic inside•Cholesterol esters have fatty acid moiety•Ex. VLDL from liver (very-low density lipoprotein)Fig. 8Fig. 33.10Nascent ChylomicronsFigs. 9,10Nascent chylomicrons from dietary TG:•SER enzymes reform the TG•Least dense lipoproteins (lot of TG)•Proteins made on RER•Apoprotein B-48Fig. 11Apoprotein B geneB-apoprotein gene encodes two polypeptides:•ApoB-100 in liver VLDL particles•ApoB-48 in intestinal cells is only 48% length•RNA editing changed codon in mRNAIV. Lipoprotein particles transport dietary lipids in bloodAdditional proteins form mature chylomicrons:•‘Nascent chylomicrons’ exocytosed into blood• Acquire additional proteins from HDL particles• ApoCII binds enzyme LPL on cell surfaces•Lipoprotein lipases• ApoE binds receptor on liver cell for recycling Fig. 12Fate of chylomicronsFig. 13Chylomicrons from dietary lipids:•matured in blood by HDL particle interaction• Are digested at capillary wall by LPL (CII activates)• Insulin stimulates more LPL on surface•FA binds albumin in blood•FA into muscle (energy)•FA into adipose (store)• Remnants bind liver through ApoE-receptorRecycled in lysosomeOlestraOlestra is artificial fat substitute•Tastes like fat, not metabolized• sucrose with fatty acyl groups esterified on OH• resistant to hydrolysis by lipases, passes through• carries lipid-soluble vitaminsKey concepts:Key concepts:•Triacylglycerols are major fat source in diet• Lipases perform digestion, bile salts emulsify• Free fatty acids and 2-monoacylglycerol form•Micelles transport components into intestinal cells•Nascent


View Full Document

RU BL 616 - Lecture Notes

Download Lecture Notes
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...
Login

Join to view Lecture Notes and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Lecture Notes 2 2 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?