Lipoprotein-associated with carrying cholesterol from periphery tissues to liver is
METABOLISM OF HDL Synthesis: HDL is synthesized in Liver cells and also in intestinal mucosal cells. (a) Hepatic HDL * Apo-A and apo-C are synthesized by polysomes on the rough endoplasmic reticulum (ER). * They are assembled with lipids to form the nascent HDL which is released in the circulation. (b) Intestinal HDL * In a similar manner, apo-A is synthesized by polysomes on the rough endoplasmic reticulum (ER). * It is assembled with lipids to form the "nascent"- HDL which is released in circulation from intestinal mucosal cells. Difference of nascent intestinal HDL from "nascent" hepatic HDL * "Nascent" intestinal HDL contains only apo-A when it circulates, it acquires apo-C and apo-E. * "Nascent"-Hepatic HDL, on the other hand, contains both apo-A and apo-C. Note: Apo-C and apo-E are only synthesized in liver and not in intestinal mucosal cells. Scavenging action of HDL: Glomset (1968) has suggested that HDL plays a major role in the removal of cholesterol from peripheral extrahepatic tissues and transpo of this cholesterol to the liver where it is fuher metabolized. This has been called as scavenging action of HDL (reverse cholesterol transpo). METABOLISM OF HDL HDL Receptor Proteins and HDL Cycle Two types of HDL receptor proteins haven been described involved in HDL metabolism. They are: 1. HDL receptor protein--SR-B1 2. ATP-binding cassette transpoer A1 Protein (ABCA1) 1. HDL receptor protein SR-B1 The class B scavenger receptor B1 (SR-B1) has been identified recently as HDL receptor with a dual role in HDL metabolism. * In the liver, and steroidogenic tissues, it binds HDL apo-A1 and cholesteryl ester is selectively delivered to the cells, although the paicle itself, including apo-A1, is not taken up. * In the tissues: On the other hands, SR-B1 mediates the acceptance of cholesterol from the cells by HDL, which then transpos it to the liver for excretion the bile (either as cholesterol or after conversion to bile acids), the process known as reverse cholesterol transpo. Nascent HDL: Nascent HDL is made up of a bilayer of PL and free cholesterol arranged in disc-like form called as discoid HDL containing apoproteins. Formation of HDL3 by LCAT: Lecithin-cholesterol acyltransferase of plasma binds with nascent HDL discs and gets activated by A-1 and C-II apoproteins of HDL itself and transfers acyl groups from HDL-PL to the free cholesterol thus producing Lysophospholipids and cholesteryl-esters. Lysophospholipids thus formed are released from HDL to plasma where they bind to albumin and cholesteryl esters and transferred into the 'central core' of the HDL paicles. Thus by the above reactions 'Discoid HDL' is conveed to 'spherical' HDL which is called as HDL-3 paicle, which is bounded by a lipid layer with apoproteins and cholesteryl esters embedded in its core. Nascent HDL (discoidal) --- HDL-3 paicle (spherical)Ref: Textbook of Medical Biochemistry, Eighth Edition, Dr (Brig) MN Chatterjea, page no: 449
HDL
LDL
VLDL
IDL
Metabolism of lipid