LIPO PROTEIN METABOLISM

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LIPO PROTEIN METABOLISM:

LIPO PROTEIN METABOLISM Dr. V. Siva Prabodh MD Professor Dept. of Biochemistry NRI Medical College

Lipoproteins:

Lipoproteins These are molecular complexes which contains Lipids & proteins Function : Transports Lipids in blood. Classification of Lipoproteins Five Major classes Chylomicrons VLDL LDL HDL FFA with albumin

Lipo proteins are seperated by Ultra centrifugation/Electrophoresis:

Lipo proteins are seperated by Ultra centrifugation/Electrophoresis

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Chylomicrons : Synthesized in the Intestine. Transport Exogenous lipids (Dietary Lipids) 99% Lipids, 1% protein, Density very less. VLDL : Produced in the Liver & Intestine Transport Endogenous lipids

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3) LDL : Formed from VLDL in blood Transport cholesterol from Liver to other tissues. 4) HDL : Mostly synthesized in Liver Transport cholesterol from peripheral tissues to Liver (Reverse cholesterol transport) 5) FFA with albumin : Each molecule of albumin hold 20-30 molecules of FFA.

Apolipoproteins:

Apolipoproteins Structural determinants of lipoproteins Enzyme cofactors Ligands for binding to lipoprotein receptors

Apoproteins:

Apoproteins The protein forms of Lipoproteins are known as Apolipoproteins or Apoproteins. Functions: Structural component – apo A, apo B 48 , apo B 100 apo C Recognizes surface receptors – apo E, apo B 100 Activate Lipoprotein Lipase – apo C II

Chylomicrons:

Chylomicrons

VLDL:

VLDL

LDL:

LDL Low density Lipoprotein is formed from VLDL and the Intermediate is IDL. LDL contain high cholesterol and less TAG . Function :– Supply cholesterol to extra hepatic tissues. LDL particles bind to specific receptors over the cell membrane which are clathrin coated pit Apo B 100 recognizes the receptors over the cell membrane Deficiency of LDL receptors leads to Increased circulating LDL and hence cholesterol increases Eg: Type IIa hyperbeta lipoproteinemia.

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From Medical Biochemistry , Baynes & Dominiczak, Mosby, 1999.

Enzymes and Transfer Proteins:

Enzymes and Transfer Proteins LCAT (Lecithin:Cholesterol Acyltransferase) Formation of cholesterol esters in lipoproteins ACAT (Acyl-CoA:Cholesterol Acyltransferase) Formation of cholesterol esters in cells CETP (Cholesterol Ester Transfer Protein)

HDL :

HDL High density Lipoproteins (Three types HDL 1 , HDL 2, HDL 3 ) Cholesterol is transported from Extra hepatic tissue to Liver where it is excreted in the form of bile. Anti – atherogenic , Good cholesterol Intestinal cells synthesize HDL and release into blood. LCAT: Lecithin cholesterol Acyl transferases, transfer PUFA from Lecithin to cholesterol to form cholesterol ester, which moves into interior of HDL APO A I activates LCAT The HDL with more cholesterol are taken up by Liver cells, and cholesterol is released into Liver. (Reverse cholesterol transport)

HYPER LIPOPROTEINEMIAS:

HYPER LIPOPROTEINEMIAS

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From Medical Biochemistry , Baynes & Dominiczak, Mosby, 1999.

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Familial hypercholesterolemia (type II a) 1 Apo-B100 Apo-E Dominantly inherited disorder deficiency in a cell surface LDL-R (the receptor regulates LDL degradation and cholesterol synthesis ) high cholesterol (since birth) high LDL-C leads to premature atherosclerosis , xanthomas of skin and tendons T otal C holesterol >240 mg/dl LDL>190 mg/dl

Xanthomas raised lesions related to hyperlipidemia:

Xanthomas raised lesions related to hyperlipidemia Eruptive Xanthomas -generally associated with hypertriglyceridemia Xanthomas of the eyelid -generally associated with hypercholesterolemia

Case Study – familial hypercholesterolemia:

Case Study – familial hypercholesterolemia 8 yr girl Admitted for heart/liver transplant History CHD in family 2 yr xanthomas appear on legs 4 yr xanthomas appear on elbows 7 yr admitted w/ MI symptoms [TC] = 1240 mg/dl [TG] = 350 mg/dl [TC]father = 355 mg/dl [TC]mother = 310 mg/dl 2 wks after MI had coronary bypass surgery Despite low-fat diet, cholestyramine, & lovastatin, [TC] = 1000 mg/dl

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Thank you

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