B-48Chylomicrons:ATGChTriglycerides are removedB48NacentIntestinalchylomicronsfrom the chylomicrons inAdiposemucosatissueEc-lextrahepatictissuesthroughaTGCChPLpathway shared with VLDLCh048RChytomlcrorrHDLPthat involves hydrolysis by theCHACEFAChlipoprotein lipase (LPL) systemTGFA CRRChaA progressive decrease inLiverChylomicrontemnantsparticle diameter occurs asEndothelial cellstriglycerides in the core areTG:triacylglycerolsdepleted. Surface lipids, apo A.Ch: cholesterol and cholesterol estersPL:phospholipidsI, apo A-II, and apo C are:freefattyacidsFAtransferred to HDL. TheA:apo-A-l,apo-A-llandapo-A-VB-48:apo-B-48resultantchylomicronremnants:apo-c-llC-Il:apo-EEaretakenup by receptor-CRR:chylomicronremnantreceptormediatedendocytosisintoLPL::lipoproteinlipasesopyright1998.S.Marchesinihepatocytes
11 Chylomicrons: Triglycerides are removed from the chylomicrons in extrahepatic tissues through a pathway shared with VLDL that involves hydrolysis by the lipoprotein lipase (LPL) system. A progressive decrease in particle diameter occurs as triglycerides in the core are depleted. Surface lipids, apo A - I, apo A -II, and apo C are transferred to HDL. The resultant chylomicron remnants are taken up by receptor - mediated endocytosis into hepatocytes
B. Very Low Density Lipoproteins (VLDL):LiverVLDL, secreted by liver, provides aAdiposB-100TGIssuCEChPLandothemeans for export of triglycerides toChFAB-100tissuesNacettVLDCEperipheral tissues. VLDL contains apoTGAPLOB100and someapoC.MoreapoCis100ChLDHDLacquired from HDL in plasma. VLDLtriglycerides are hydrolyzed byTGChlipoproteinlipase,yieldingfreefattyChPlooLacids for storage in adipose tissue andEndothelial cellsforoxidationintissuessuchascardiacand skeletal muscle. The resultingdepletionoftriglycerides producesTG:triacyglycerolsremnantstermed IDL.Some oftheCh: cholesterol and cholesterol estersPL:phospholipidsIDL particles are endocytosed directlyFA:freefatty acidsby the liver. The remainders areA:apo-A-l,apo-A-llandapo-A-VB-48:apo-B-48converted toLDL by further removalc-ll:apo-c-llof triglycerides mediated by hepaticE:apo-Elipase.CRR:chyomicron remnantreceptorLDL-R:LDLreceptor
12 B. Very Low Density Lipoproteins (VLDL): VLDL, secreted by liver, provides a means for export of triglycerides to peripheral tissues. VLDL contains apo B100 and some apoC. More apoC is acquired from HDL in plasma. VLDL triglycerides are hydrolyzed by lipoprotein lipase, yielding free fatty acids for storage in adipose tissue and for oxidation in tissues such as cardiac and skeletal muscle. The resulting depletion of triglycerides produces remnants termed IDL. Some of the IDL particles are endocytosed directly by the liver. The remainders are converted to LDL by further removal of triglycerides mediated by hepatic lipase
C. Low-Density Lipoproteins (LDL):shuntBasicPathways inLDLRegulationopo8-100VLDLVLDLLipolysisProductionLiverVLDLRemnantopoEapoC.Shunt PathwayLDLClearanceConversionOther Sites,IncludingCoronaryArteriesLDL3
13 C. Low-Density Lipoproteins (LDL): shunt
Low-Density Lipoproteins (LDL):LiverAdiposB-100TGIssueA major pathway by which LDLSCEChAandotheChFAB-100tissuesis catabolized in hepatocytes andNEdentVLDCETGmost othernucleatedcellsinvolveAPPL100Chhigh-affinityreceptor-mediatedLDHDLendocytosis.Cholesteryl estersfromthe LDL core are then hydrolyzedTGChChPLyielding free cholesterol for the100B100IDIsynthesis of cell membranes. CellsEndothelial cellsalsoobtaincholesterolbydenovosynthesis via a pathway involvingthe formation of mevalonic acid byTG:triacyglycerolsCh: cholesterol and cholesterol estersHMG-CoAreductase.ProductionofPL:phospholipidsthisenzymeandofLDLreceptorsisFA:freefatty acidsA:apo-A-l,apo-A-llandapo-A-Vregulated atthetranscriptionallevelB-48:apo-B-48by the content ofcholesterolin thec-ll:apo-c-llE:apo-Ecell.CRR:chyomicronremnantreceptorLDL-R:LDLreceptor
14 Low-Density Lipoproteins (LDL): A major pathway by which LDL is catabolized in hepatocytes and most other nucleated cells involve high-affinity receptor-mediated endocytosis. Cholesteryl esters from the LDL core are then hydrolyzed, yielding free cholesterol for the synthesis of cell membranes. Cells also obtain cholesterol by de novo synthesis via a pathway involving the formation of mevalonic acid by HMG-CoA reductase. Production of this enzyme and of LDL receptors is regulated at the transcriptional level by the content of cholesterol in the cell
D. Lp (a) Lipoprotein:1. Lp (a) is a heterogeneouso0aamacromoleculeassociatedwithearly myocardial infarction2coronary artery disease, andstroke2. The structure of Lp (a)HOOCconsists of an apolipoproteinHODOmolecule linked to apo B- 100onalipid-richLDLcore.Lp(a)Kningle-4 domain0000lipoprotein is formed from anKingle-5domainLDL-like moiety and the Lp(a)Protease donainprotein linked by a disulfideCarbohydrataWApoB-100bridge.Structureof Lp (a)3.The level of Lp(a) is genetically controlled4. Apo (a) has a strong structural homology to plasminogen, but lacks theabilityto be activated by tissue plasminogenactivator15
15 1. Lp (a) is a heterogeneous macromolecule associated with early myocardial infarction, coronary artery disease, and stroke 2. The structure of Lp (a) consists of an apolipoprotein molecule linked to apo B- 100 on a lipid-rich LDL core. Lp(a) lipoprotein is formed from an LDL-like moiety and the Lp(a) protein linked by a disulfide bridge. 3. The level of Lp(a) is genetically controlled 4. Apo (a) has a strong structural homology to plasminogen, but lacks the ability to be activated by tissue plasminogen activator. D. Lp (a) Lipoprotein: