Metabolisme Kolesterol, Lipoprotein Dan Apolipoprotein

METABOLISME KOLESTEROL, LIPOPROTEIN DAN APOLIPOPROTEIN Meizly Andina DEPARTEMEN BIOKIMIA FAKULTAS KEDOKTERAN UNIVERSITAS MUHAMMADIYAH SUMATERA  Cholesterol is present in tissues and in plasma either as: ▪ Free cholesterol or ▪ as a storage form, combined with a long-chain fatty acid as cholesteryl ester.   In plasma, both forms are transported in lipoproteins Cholesterol is an amphipathic lipid and as such is an essential structural component of membranes and of the outer layer of plasma lipoproteins.  Cholesterol is obtained from  the diet  or synthesized by a pathway that occurs in most cells of the body,  but to a greater extent in cells of the liver and intestine.  amino acids. which can be produced  from glucose  fatty acids. .The precursor for cholesterol synthesis is acetyl CoA. Metabolisme cholesterol Fungsi cholesterol :  Membentuk garam empedu  Integritas membran  Membentuk hormon steroid  Membentuk Vitamin D3 . Absorpsi dan transportasi lipid  Free Fatty acids.monoacylglycerol .  Lipid lainnya ditransport oleh Chylomicron didalam pembuluh .  Resintesa TG dan Cholesteryl ester didalam sel-sel mucosa usus  Enzim Fatty acyl CoA synthetase (Thiokinase) mengaktifkan FA  FA rantai sedang dan pendek langsung ke sirkulasi porta dan ditransport oleh Albumin. free cholesterol dan 2. Cholesterol non . ditransport oleh VLDL  Dihydrolisa oleh Lipoprotein lipase IDL LDL (22 nm.Transportasi lipid  TG dari Chylomicron dihydrolisa oleh enzim Lipoprotein lipase Chylomicron remnant.  Hepar mensynthese TG. ±1500 molekul ester Cholesterol dng Linolat)  LDL diselubungi oleh : . memp.Phospholipid . ini diesterifikasi dan oleh protein transfer .kontrol synthese de novo cholesterol di jaringan  HDL : transport cholesterol dari jaringan rusak/mati kesirkulasi. Oleh Acyltransferase cholest.transport cholesterol ke jaringan peripher .Transportasi lipid  Fungsi LDL : . Lipoprotein general structure  Lipoproteins are characterized according to their densities. These proteins are referred to as apoproteins.  The free hydroxyl group of cholesterol is exposed on the surface of the lipoprotein to interact with water. .  The lipoprotein densities vary depending on their lipid composition. They are important in : 1. Regulaton certain enzymes which act on lipoproteins 3. Maintaining the structural integrity of the lipoproteins 2.APOLIPOPROTEINS Apolipoproteins are the protein components of the lipoproteins. Receptor recognition . Properties of Some Human Apolipoproteins . STRUCTURE OF LIPOPROTEIN . Composition of the Lipoproteins in Plasma of Humans . Lipoprotein Composition . LIPOPROTEIN FUNCTIONS . and LDL. HDL. VLDL. 20 to 25 nm. 50 to 200 nm in diameter. 28 to 70 nm. . Chylomicrons.Four classes of lipoproteins. visualized in the electron microscope after negative staining. 8 to 11 nm. The diameter of chylomicrons ranges from about 100 to 500 nm. Several apolipoproteins that protrude from the surface (B-48. with head groups facing the aqueous phase. C-II) act as signals in the uptake and metabolism of chylomicron contents. Triacylglycerols sequestered in the interior (yellow) make up more than 80% of the mass. large sized. Synthesized in small intestine Transport dietary lipids 98% lipid. lowest density Apo B-48  Receptor binding  Apo C-II  Lipoprotein lipase activator  Apo E  Remnant receptor binding     .Molecular structure of a chylomicron • The surface is a layer of phospholipids. C-III. example : 1. Lipoprotein lipase releases free fatty acids and glycerol from chylomicrons and VLDL into the tissues 2. Lechitin cholesterol acyl transferase .LIPOPROTEIN METABOLISM The two key enzyme systems are involved in lipoprotein metabolism. C. phospholipid. LDL receptorrelated protein. apolipoprotein B-48.Metabolic fate of chylomicrons. HDL. E. B-48. apolipoprotein E. HL. . high-density lipoprotein. apolipoprotein A. P. (A. TG. apolipoprotein C. LRP. cholesterol and cholesteryl ester. triacylglycerol. hepatic lipase. .) Only the predominant lipids are shown.  It is mostly made in the body (90%) with a small portion (10%) derived from the diet.VERY LOW DENSITY LIPOPROTEIN (VLDL)  Very low density lipoprotein (VLDL) is formed in the liver from triacylglycerol and cholesterol provided by the tissue and with the assistance of apoprotein B-100. . . . as in chylomicrons. . the VLDL molecule contains the apoproteins needed for both VLDL and LDL functions.  The role of VLDL is to transport and deliver fatty acids to peripheral tissues.LIPID MOBILIZATION  The VLDL is exported and picks up apoprotein CII and E in the blood. Triacylglycerols contained in VLDL. Note that since LDL is derived from VLDL. are substrates for lipoprotein lipase in capillaries.  The fatty acids are taken up by the cells in these tissues and are either used in the production of energy (skeletal and cardiac muscles) or used in the synthesis of tissue or milk fat (adipose tissues and lactating mammary glands. .LIPID mature MOBILIZATION VLDL reaches the peripheral  The tissues (adipose tissue and skeletal and cardiac muscles) where it is acted upon by the enzyme plasma lipoprotein lipase (LPL) which needs apoCII for its activation.  The action of this enzyme results in hydrolysis of triglycerides into glycerol and free fatty acids. the VLDL returns the apoC back to the HDL and become VLDL remnants (IDL).  Then VLDL remnants give their apoE back to the HDL and become LDL. . After LIPID MOBILIZATION losing the main bulk of its triglycerides. LIPID MOBILIZATION . Characteristics of Common Hyperlipidemia . Clinical Manifestations of Hyperlipidemia Xanthelasma Severe xanthelasma and arcus cornea Tuberous xanthoma Large tuberous xanthoma of elbow Eruptive xanthoma Xanthoma of extensor tendons of the hands Xeroradiogram of Achilles tendon xanthoma Xanthoma of Achilles tendon . Lipoprotein Metabolism and Atherosclerosis . Atheroma in Artery . Log-linear relationship between LDL-C levels and relative risk for CHD . Sekian … .