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Papers In Press, published online ahead of print September 16, 2002
J. Lipid Res., doi:10.1194/jlr.M200293-JLR200
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Submitted on July 26, 2002
Medical Laboratory Sciences and Technology, Karolinska Institute, Stockholm S14186
Corresponding Author: Ingemar.Bjorkhem{at}chemlab.hs.sll.se
Oxysterols possess powerful biological activities. Some of their effects on the regulation of key enzymes are similar to those of cholesterol, but are much more potent.One of the critical properties of oxysterols is their ability to pass lipophilic membranes at a high rate. Transfer of unesterified 25-hydroxycholesterol from red blood cells to plasma has been reported to occur more than 1000 times faster than cholesterol. Here we have measured the relative rate of such translocation of the three major oxysterol in human circulation: 27-hydroxycholesterol, 24S-hydroxycholesterol and 4
Revised on September 11, 2002
Accepted on September 11, 2002
On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation: Critical importance of the oxygen function
-hydroxycholesterol. The distance from the 3-hydroxyl group to the additional hydroxyl group is the greatest possible in 27-hydroxycholesterol and the least possible in 4-hydroxycholesterol. The rate of exchange between erythrocytes and plasma was found to be high for 27-hydroxycholesterol and 24S-hydroxycholesterol and hardly possible to measure for 4-hydroxycholesterol and cholesterol. When injected intravenously into humans, deuterium labelled 24- and 27-hydroxycholesterol caused an immediate high enrichment of the corresponding plasma sterols followed by a decay. After injection of labelled 4-hydroxycholesterol, the maximum deuterium enrichment occurred after 2-3 h, when secretion of the oxysterol from the liver is likely to be the limiting factor. When radio-labelled cholesterol was injected under the same conditions, maximum appearance of label occurred after about 2 days. The results illustrate the importance of the position of the additional oxygen in oxysterols and are discussed in relation to the rate of metabolism and biological effects of these oxysterols.
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