The role of LCAT and cholesteryl ester transfer proteins for the HDL and LDL structure and metabolism.
Since the early detection of LCAT by Glomset, a great deal of research has been conducted for establishing the role of this enzyme in the Lp metabolism. It became apparent that LCAT produces more than 3/4 of the CE found in plasma. LCAT acts primarily on Lp with high PC/FC contents and high PC/FC ratios. For expression of the full activity, apo-Lp cofactors such as apo-AI, -CI, -AIV and -E are necessary. Although it was believed for a long time that HDL are the only substrate for LCAT we could demonstrate that LDL and even apoA/C/E free LpB is utilized by LCAT. The CE formed in PC/FC rich Lp are transferred to VLDL and LDL by specific proteins, which also promote the exchange of CE against TG. TG in these particles are hydrolyzed by liver lipase providing new space in the core for further cholesterol esterification. Thus LCAT exerts its physiological role in concert with other enzymes e.g. LPL, hepatic lipase and possibly phospho-lipases as well as with exchange and transfer processes partly catalyzed by specific exchange/transfer proteins. The main function of LCAT without doubt is the reverse cholesterol transport from periphery to liver counteracting the accumulation of CE in reticulo endothelial cells by the scavenger pathway. Metabolic studies revealed that the cholesterol clearance from the circulation proceeds in the same order of magnitude as the esterification by LCAT takes place. This possibly implies that LCAT might be the rate limiting enzyme for cholesterol catabolism from blood.
D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood / Q000502:physiology*; D011487:Protein Conformation; D013552:Swine
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase