SR‐BI and HDL Cholesteryl Ester Metabolism

Abstract

Scavenger receptor class B, type I (SR‐BI) is the receptor for high density lipoprotein (HDL) that mediates cellular uptake of HDL cholesteryl ester (CE) and is a major route for cholesterol delivery to steroidogenic pathways. SR‐BI is localized in specialized microvillar channel plasma membrane compartments that retain HDL and are sites for HDL CE selective uptake. In fact, adrenal gland microvillar channel formation is regulated by adrenocorticotropin hormone and requires SR‐BI expression. SR‐BI‐mediated uptake of HDL CE is a two‐step process requiring high affinity HDL binding followed by transfer of CE to the membrane. SR‐BI delivers HDL CE to sites in the membrane where it is readily metabolized to free cholesterol by cell type‐specific neutral CE hydrolases. The most likely candidate for the hydrolysis of HDL CE delivered via SR‐BI in the adrenal gland is hormone sensitive lipase. New data in adrenocortical cells as well as the study of a mutant SR‐BI receptor lend insight into the mechanism of cholesterol transfer from plasma HDL to the steroidogenic pathway in endocrine cells.

• Scavenger receptor class B
• Type I (SR‐BI)
• CD36
• Selective uptake pathway
• High density lipoprotein (HDL)
• Low density lipoprotein (LDL)
• Low density lipoprotein receptor (LDLR)
• Cholesteryl ester (CE)
• Free cholesterol (FC)
• Selective uptake (SU)
• Adrenocorticotrophic hormone (ACTH)
• Phosphatidylcholine (PC)
• Hormone sensitive lipase (HSL)

Acknowledgments

This research was supported by NIH grants HL58012 and HL63768 and an Atorvastatin Research Award (A.R.A.) to M.A.C. sponsored by Pfizer, Inc. The authors would like to acknowledge Drs. Fayanne E. Thorngate and George H. Rothblat for critical review of this manuscript. This paper is submitted in memoriam of Dr. David L. Williams who passed away in July of this year. His good humor, kindness, and keen scientific insight will be sorely missed by all those who had the privilege of knowing and working with him.