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

Expression of the gene coding for the synthesis of 25(R),26-hydroxycholeste rol in many tissues and the finding that this sterol can:be the sole pathwa y for the production of bile acids have led to a renewed interest in this m etabolic pathway. A further impetus for exploring the normal biologic roles that are served by expression of the CYP27A1 gene is the knowledge that mu tations in humans are associated with accelerated atherosclerosis and with severe neurologic impairment. The molecular mechanisms governing these phen otypic expressions are not known but in light of the traditional role of st eroids as ligands for receptors that regulate gene expression it seems like ly that the intermediates in this pathway modulate a number of enzymatic ac tivities that remain to be elucidated. (C) 2000 Elsevier Science B.V. All r ights reserved.