Novel routes for metabolism of 7-ketocholesterol.
Oxysterols (oxygenated forms of cholesterol) are present at low levels in the circulation and accumulate is plasma and tissues in some pathologies. In atherosclerotic lesions, 7-oxygenated oxysterols, predominantly 7-ketocholesterol, accumulate and have been implicated in the pathology of the disease. Therefore, knowledge of the mechanisms for 7-ketocholesterol generation and metabolism may provide therapeutic drug targets. There is some in vivo and in vitro evidence that sterol 27-hydroxylase acts on 7-ketocholesterol to initiate its degradation to more polar, water-soluble products. Recent studies indicate an alternative mechanism, in which 7-ketocholesterol is reduced to 7 beta-hydroxycholesterol by 11 beta-hydroxysteroid dehydrogenase type 1.
Jessup
Wendy
W
Centre for Vascular Research at School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. w.jessup@unsw.edu.au
Brown
Andrew J
AJ
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase; D006801:Humans; D007653:Ketocholesterols / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism
D007653:Ketocholesterols; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C003001:7-ketocholesterol