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Main lipids in the blood are the triglycerides and cholesterol. Insoluble in the water. Transport in the blood is via lipoproteins
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TRIGLYCERIDES Glycerol with 3 attached fatty acids Exogenous source : Dietary Endogenous : Liver and tissue storage 95 % of body fat is triglycerides Energy source when plasma glucose is decreased Triglyceride catabolism is regulated by lipase, epinephrine and cortisol Triglycerides transported by Chylomicrons ( exogeneous ) and VLDL ( endogenous )
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CHOLESTEROL Found only in animals Important component of membranes, steroid hormones, bile and Vitamin D Exogeneous cholesterol comes from diet Endogeneous cholesterol is synthesized by the liver 70 % of cholesterol associated with cellular components 30 % is in the plasma ( ⅓ free form, ⅔ esterfied ) Transported by HDL and LDL 4
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Fatty acids are short to long carbon chained molecules Saturated fatty acids Unsaturated fatty acids Phospholipids Important components of cell membranes Lecithin and sphingomyelin are utilized to determine fetal lung maturity from amniotic fluid ( L / S Ratio ) Glycolipids Lipids with a carbohydrate component ABO antigen are glycolipids
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Lipoprotein is a complex spherical structure that has a hydrophobic core wrapped in hydrophilic coating. 4 major classes of lipoproteins. Chylomicrons Very low density lipoproteins (VLDL) Low density lipoproteins (LDL) High density lipoproteins (HDL)
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Class Diameter (nm) % protein % cholesterol % phospholipid % triacylglycerol & cholesterol ester HDL5–153330294 LDL18–282550218 IDL25–5018292231 VLDL30–8010221850 Chylomicrons100-1000<28784
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Most core lipid in LDL is cholesterol ester. ApoB100 is only apolipoprotein in the surface.
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Also named as apoB-100/apoE receptors LDL receptors exist in the liver and in most peripheral tissues The complexes of LDL and receptor are taken into the cells by endocytosis, where LDL is degraded but the receptors are recycled Number and function of the receptor shows LDL levels. LDL cholesterol levels are positively related to risk of cardiovascular disease Therefore, cholesterol in LDL has been called “bad cholesterol”
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APOLIPROPROTEINS Outer protein “shell” of the lipoprotein molecule The protein – lipid interaction allows the water insoluble lipid to become soluble in plasma 12
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A, B, C, D, E are major classes Subclasses: apo A-1, apo C-II N.B. function of all apolipoproteins are not yet known Act as structural components of lipoproteins Recognize the lipoprotein receptors on cell membrane surface as ligand Activate/inhibit enzymes involved in lipoprotein metabolism
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Exogenous Endogenous Lipoprotein lipase release FFA and glycerol from chylomicron and VLDL Lecithin Cholesterol acyl transferase LCAT Forms cholesteryl esters from free cholesterol and fatty acids
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Serum lipoprotein concentrations differ between adult men and women, Primarily as a result of differences in sex hormone levels, Women having, on average, higher HDL cholesterol levels and lower total cholesterol and triglyceride levels than men. The difference in total cholesterol, however, disappears after menopause as estrogen decreases
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Familial hypercholesterolemia (FH) (7.5- 12 mmol/L) Primarily LDL elevations Synthesis may be normal but decrease or lack LDL receptors due to mutation in LDL receptor gene. Therefore LDL builds-up in serum Since cells cannot acquire from LDL therefore increase internal synthesis of cholesterol. Tendon xanthomatas Early occurrence of coronary artery disease M. Zaharna Clin. Chem. 2009 18
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Triglycerides Borderline = 150-200 mg/ dl High 200-500 mg/dl Very High > 500 mg/dl Familial hypertriglyceridemia Genetic Secondary hypertriglyceridemia Hormonal imbalances Imbalance between synthesis and clearance of VLDL M. Zaharna Clin. Chem. 2009 19
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Generally caused by deficiency of LPL or LPL cofactor. (LPL hydrolyzes triglycerides in chylomicrons and VLDL) Deficiency prevents processing and clearing of triglycerides Elevated even with fasting M. Zaharna Clin. Chem. 2009 20
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Presence of elevated levels of serum total cholesterol and triglycerides Hepatic overproduction of apo B Increased VLDL and LDL M. Zaharna Clin. Chem. 2009 21
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Genetic mutation of LPL or apo C-II gene Recurrent abdominal pain Pancreatitis
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Primary Secondary
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DiseaseLipid abnormality DMTG AlcoholTG CRFTG Drugs thiazideTG HypothyroidismCholesterol Nephrotic syndromeCholesterol
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