Computational Modeling of Hepatic Lipid and Lipoprotein Metabolism
Lipid Transport Lipoprotein Structure and Function.
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Transcript of Lipid Transport Lipoprotein Structure and Function.
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Lipid Transport
Lipoprotein Structure and Function
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Plasma LipoproteinsStructurefigure 19-1
LP core Triglycerides Cholesterol
esters LP surface
Phospholipids Proteins cholesterol
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Plasma LipoproteinsClasses & Functions
Chylomicrons Synthesized in small
intestine Transport dietary lipids 98% lipid, large sized,
lowest density
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Plasma LipoproteinsClasses & Functions
Very Low Density Lipoprotein (VLDL) Synthesized in liver Transport
endogenous triglycerides
90% lipid, 10% protein
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Plasma LipoproteinsClasses & Functions Intermediate Density
Lipoprotein (IDL) Synthesized from VLDL during VLDL
degradation
Triglyceride transport and precurser to LDL
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Plasma LipoproteinsClasses & Functions
Low Density Lipoprotein (LDL) Synthesized from IDL Cholesterol transport 78% lipid, 58%
cholesterol & CE
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Plasma LipoproteinsClasses & Functions
High Density Lipoprotein (HDL)
Synthesized in liver and intestine
Reservoir of apoproteins Reverse cholesterol transport 52% protein, 48% lipid, 35%
C & CE
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Heterogeneity of LDL-particles Not all LDL-particles the same
Small dense LDL (diameter <256A) Large buoyant LDL (diameter >256 A) Lamarche B, St-Pierre AC, Ruel IL, et al. A prospective,
population-based study of low density lipoprotein particle size as a risk factor for Can J Cardiol 2001;17:859-65.
2057 men with hi LDL, 5 year follow-up Those with elevated small dense LDL had RR of 2.2 for IHD
compared to men with elevated large buoyant LDL Detection expensive Treatment for lowering small dense LDL similar to
lowering all LDL (diet, exercise, drugs) Some drugs (niacin, fibrates) may be more effective at
lowering small dense LDL.
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HDL : Functions Apoprotein exchange
provides apo C and apo E to/from VLDL and chylomicrons
Reverse cholesterol transport
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Reverse cholesterol transportfigure 19-6
Uptake of cholesterol from peripheral tissues (binding by apo-A-I)
Esterification of HDL-C by LCAT
LCAT activated by apoA1 Transfer of CE to
lipoprotein remnants (IDL and CR) by CETP
removal of CE-rich remnants by liver, converted to bile acids and excreted
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