title: Cholesteryl ester transfer proteins from different species do not have equivalent activities.
abstract: Site-specific changes in the amino acid composition of human cholesteryl ester transfer protein (CETP) modify its preference for triglyceride (TG) versus cholesteryl ester (CE) as substrate. CETP homologs are found in many species but little is known about their activity. Here, we examined the lipid transfer properties of CETP species with 80-96% amino acid identity to human CETP. TG/CE transfer ratios for recombinant rabbit, monkey, and hamster CETPs were 1.40-, 1.44-, and 6.08-fold higher than human CETP, respectively. In transfer assays between VLDL and HDL, net transfers of CE into VLDL by human and monkey CETPs were offset by equimolar net transfers of TG toward HDL. For hamster CETP this process was not equimolar but resulted in a net flow of lipid (TG) into HDL. When assayed for the ability to transfer lipid to an acceptor particle lacking CE and TG, monkey and hamster CETPs were most effective, although all CETP species were able to promote this one-way movement of neutral lipid. We conclude that CETPs from human, monkey, rabbit, and hamster are not functionally equivalent. Most unique was hamster CETP, which strongly prefers TG as a substrate and promotes the net flow of lipid from VLDL to HDL.
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Morton
authors.forename: Lahoucine
authors.initials: L
authors.lastname: Izem
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D057809:HEK293 Cells; D000882:Haplorhini; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D011817:Rabbits; D013045:Species Specificity; D013379:Substrate Specificity; D014280:Triglycerides / Q000378:metabolism
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008074:Lipoproteins; D014280:Triglycerides
keywords: TP2 antibody; high density lipoprotein; thimerosal inhibition; triglyceride; unidirectional lipid transfer; very low density lipoprotein