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What is In cholesterol transport which is not needed - and explain in detail?
Ans. is 'b' i.e.. Kidney o Dietary cholesterol is transported from intestine to liver by chylomicron-chylomicron remnant system,o From liver cholesterol is in corporated into VLDL and is distributed to extrahepatic tissues (like adipose tissue) through LDL (i.e. after conversion of VLDL into LDL).o HDL transports cholesterol from extra-hepatic tissues (blood vessels, adipose tissue) to liver.o VLDL carries endogenous triglycerides (triglycerides from liver to extrahepatic tissues).o Chylomicrons carry exogenous (dietiy) triglycerides to extrahepatic tissues and remaining triglyceride to liver through chylomicron remnants.Transport of lipidso There are two pathways of lipid transport in the body -1. Transport of dietry lipid (Exogenous pathway)o It is the transport of lipid from intestine to liver.o Chylomicrons transport the dietry lipid from intestine to liverr.o In diet the major lipids are triglyceride and cholesterol.o Cholesterol is absorbed as such in proximal small intestine and is esterified to cholestery! ester (ChE). Triglycerides are hydrolysed by lipases to glycerol and fatty acids which are absorbed in intestine.o Inside intestinal cells triglyceride is synthesized by fatty acids. Chylomicrons are synthesized in the small intestine that contain triglyceride, cholesteryl ester, cholesterol, phosphlipids, and apoprotein B-48 (apo B-48) and apo-A.o These chylomicrons are secreted in the intestinal lymph and reach the systemic circulation via thoracic duct.o In the circulation apo E and apo C are transfered to chylomicrons by HDL, so now chylomicrons contain apo A, apo B-48, apo- E, & apo-C.o In the circulation, triglycerides of chylomicrons are hydrolysed by lipoprotein lipase (LPL) present on endothelial cells of vessels of skeletal muscles, adipose tissue and heart, but not in liver.o The released fatty acids are utilized locally by these tissues.o Adipose tissue uses these fatty acids to restore them as TGs and heart and skeletal muscle use them as source of energy.o Thus, function of chylomicrons is to transport exogenous (dietry)triglyceriderto adipose tissue (for storage), heart (for energy) and muscle (for energy).o The chylomicron particle progressively shrinks in size by action of LPL and, cholesterol, phospholipids, apo-A and apo C are transferred to HDL, creating chylomicron remnants that contains more cholesterol, less triglycerides, apo-E & apo B-48.o Chylomicron remnants are removed by liver bv the LDL receptors that require apo-E as ligand.2. Transport of Hepatic lipids (Endogenous pathway)o VLDL is synthesized in liver that contains high triglyceride, ChE, cholesterol, phospholipid and Apo B-100. (VLDL particles resemble chylomicrones in composition except that VLDL contains Apo B-100 instead of Apo B-48).o VLDL particles are secreted in the plasma and as with chylomicron, Apo E and Apo C are transferred from HDL to VLDL. Now VLDL contains Apo B-100, Apo E and Apo C.o In plasma, triglycerides of VLDL are hydrolysed by same lipoprotein lipase (see above) and apo C is transferred to HDL and the remmants are called IDL.o 40-60% of IDL is removed by liver via LDL receptor mediated endocytosis, this process require Apo E which acts as ligand for LDL receptors.o Remaining IDL is remodeled by hepatic lipase which hydrolyzes more triglyceride to form LDL that contains maximum cholesterol.o 70% of LDL is removed by liver via LDL receptor and 30% is utilized by peripheral tissues as a source of cholesterol.o Lecithine-Cholesterol acetyltransferase (LCAT) esterifes cholesterol in HDL during reverse cholesterol transport,o All nucleated cells in different tissues synthesize cholesterol, but the excretion of cholesterol is mainly by liver in the bile or by enterocytes in gut lumen. So, cholesterol must be transported from peripheral tissue to liver for excretion2. This is facilitated by HDLQ and is called reverse cholesterol transport because it transports the cholesterol in reverse direction to that is transported from liver to peripheral tissues through VLDL --> LDL cycle.Processo HDL is synthesized in liver and smalt intestine. Nascent HDL contain phospholipids and unesterified cholesterol and Apo-Ar, C, E. This nascent HDL is secreted into circulation where it acquires additional unesterified cholesterol from peripheral tissues. Within the HDL particle, the cholesterol is esterified by lecithin - cholesterol acetyltransferase (LCAT) to form cholesteryl ester and additional lipid are transported to HDL from VLDL and chylomicrons. Apo-A, activates LCATr.o There are twro pathway by which this cholesterol is transported to liver.Indirect pathwayo Cholesteryl ester is tranfered from HDL to VLDL and chylomicrons in exchange with triglyceride by the cholesteryl ester transfer protein (CETP).o This cholesteryl ester is then transported to liver (see previous explanation).Direct pathwayo HDL cholesterol can also be taken up directly by hepatocytes via the scavenger receptors class BI (SR - BI).