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.
Highlights
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
Human CETP purified from plasma and that secreted by HEK cells comigrated, suggesting HEK cells glycosylate CETP to a similar extent as occurs in vivo
The lower apparent molecular weight of hamster CETP likely results from decreased glycosylation because this CETP species lacks two of the four predicted N-linked glycosylation sites found in human CETP [22]
Summary
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. It seems likely that CETP from common experimental models such as hamster and rabbit, which have only ف80% identity to human CETP at the amino acid level, may have unique lipid transfer properties. The purpose of this study was to characterize the lipid transfer properties of CETP from three species (monkey, rabbit, and hamster) and compare them to human CETP. We have determined the relative preference of each CETP for CE and TG as a substrate and assessed their abilities to promote net TG and CE transfer between lipoproteins Such processes are central to CETP’s role in facilitating lipoprotein metabolism. We show species-specific differences in the lipid transfer properties of CETPs in terms of their substrate preference and their ability to promote net lipid transfer between lipoproteins, and between lipoproteins and model membrane surfaces
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
