Biologic role(s) of the 25(R),26-hydroxycholesterol metabolic pathway

Expression of the gene coding for the synthesis of 25(R),26-hydroxycholesterol in many tissues and the finding that this sterol can:be the sole pathway for the production of bile acids have led to a renewed interest in this metabolic pathway. A further impetus for exploring the normal biologic roles that are served by expression of the CYP27A1 gene is the knowledge that mutations in humans are associated with accelerated atherosclerosis and with severe neurologic impairment. The molecular mechanisms governing these phenotypic expressions are not known but in light of the traditional role of steroids as ligands for receptors that regulate gene expression it seems likely that the intermediates in this pathway modulate a number of enzymatic activities that remain to be elucidated. (C) 2000 Elsevier Science B.V. All rights reserved.