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Physiological Reviews, Vol. 80, No. 1, January 2000, pp. 361-554
Copyright ©2000 by the American Physiological Society
Departments of Biochemistry and Cell Biology and of Chemistry, Rice University, Houston, Texas
Schroepfer Jr., George J.
Oxysterols: Modulators of Cholesterol Metabolism and Other
Processes. Physiol. Rev. 80: 361-554, 2000.
Oxygenated derivatives of cholesterol
(oxysterols) present a remarkably diverse profile of biological
activities, including effects on sphingolipid metabolism, platelet
aggregation, apoptosis, and protein prenylation. The most notable
oxysterol activities center around the regulation of cholesterol
homeostasis, which appears to be controlled in part by a complex series
of interactions of oxysterol ligands with various receptors, such as
the oxysterol binding protein, the cellular nucleic acid binding
protein, the sterol regulatory element binding protein, the LXR nuclear
orphan receptors, and the low-density lipoprotein receptor.
Identification of the endogenous oxysterol ligands and elucidation of
their enzymatic origins are topics of active investigation. Except for
24,25-epoxysterols, most oxysterols arise from cholesterol by
autoxidation or by specific microsomal or mitochondrial oxidations,
usually involving cytochrome P-450 species. Oxysterols are
variously metabolized to esters, bile acids, steroid hormones,
cholesterol, or other sterols through pathways that may differ
according to the type of cell and mode of experimentation (in vitro, in
vivo, cell culture). Reliable measurements of oxysterol levels and
activities are hampered by low physiological concentrations
(~0.01-0.1 µM in plasma) relative to cholesterol (~5,000
µM) and by the susceptibility of cholesterol to autoxidation, which
produces artifactual oxysterols that may also have potent
activities. Reports describing the occurrence and levels of
oxysterols in plasma, low-density lipoproteins, various
tissues, and food products include many unrealistic data resulting from
inattention to autoxidation and to limitations of the analytical
methodology. Because of the widespread lack of appreciation for the
technical difficulties involved in oxysterol research, a rigorous
evaluation of the chromatographic and spectroscopic methods used in the
isolation, characterization, and quantitation of oxysterols has
been included. This review comprises a detailed and critical assessment
of current knowledge regarding the formation, occurrence, metabolism,
regulatory properties, and other activities of oxysterols in
mammalian systems.
Deceased December 11, 1998.
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