Sterol regulators of cholesterol homeostasis and beyond: The oxysterol hypothesis revisited and revised

Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

“…Lanosterol, the first sterol intermediate in cholesterol biosynthesis, is synthesized via condensation of isoprene to squalene and subsequent oxidation of squalene to MOS, followed by cyclization of MOS. 24,25-EC is generated de novo by a shunt of the cholesterol biosynthetic pathway through synthesis of 2,3;22,23-diepoxysqualene (DOS) from MOS (29). When CHO-K1 cells were metabolically labeled with [ 14 C]acetate, synthesis of MOS, cholesterol, and 24,25-EC was apparently reduced upon elevation of plasmalogens (Fig.…”

Cholesterol through the Looking Glass

“…Cholesterol Esterification-Cells were labeled with 1 Ci of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate (specific activity 56.0 mCi/mmol; American Radiolabeled Chemicals) for 4 h during treatment. Lipid extracts were analyzed for cholesteryl [ 14 C]esters by thin layer chromatography (TLC) followed by phosphorimaging, as described previously (29).…”

“…In addition, certain oxysterols and intermediates in cholesterol synthesis also participate in cholesterol homeostasis (12), for example, by inhibiting SREBP activation (13) and by accelerating the Insigdependent proteasomal degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), another key cholesterol biosynthetic enzyme (14,15).…”

A Plant Oxysterol as a regulator of glucose homeostasis

“…Oxysterols reportedly diminished the rate of cholesterol biosynthesis being a potent inhibitor even at 10-9 M, though cholesterol itself was weakly inhibitory at 10-5 M [6]. It is believed that the presence of a large excess of cholesterol (100 fold) in vivo reduced oxysterol binding affinity to nuclear receptors, whereas high affinity binding to receptors were noted in vitro [7]. .…”