On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation

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 1,000 times faster than cholesterol. Here we have measured the relative rate of such translocation of the three major oxysterols in human circulation: 27-hydroxycholesterol, 24S-hydroxycholesterol, and 4β-hydroxycholesterol. The distance from the 3β-hydroxyl group to the additional hydroxyl group is the greatest possible in 27-hydroxycholesterol and the least possible in 4β-hydroxycholesterol. The rate of exchange between erythrocytes and plasma was found to be high 27-hydroxycholesterol and 24S-hydroxycholesterol, and possible to and cholesterol. and 27-hydroxycholesterol high of the plasma a of the of the from the is to be the was the of the of the of the additional in oxysterols and are in to the rate of and biological effects of 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 1,000 times faster than cholesterol. Here we have measured the relative rate of such translocation of the three major oxysterols in human circulation: 27-hydroxycholesterol, 24S-hydroxycholesterol, and 4β-hydroxycholesterol. The distance from the 3β-hydroxyl group to the additional hydroxyl group is the greatest possible in 27-hydroxycholesterol and the least possible in 4β-hydroxycholesterol. The rate of exchange between erythrocytes and plasma was found to be high 27-hydroxycholesterol and 24S-hydroxycholesterol, and possible to and cholesterol. and 27-hydroxycholesterol high of the plasma a of the of the from the is to be the was the of The the of the of the additional in oxysterols and are in to the rate of and biological effects of Oxysterols are of have been in of of and One of their and is in of of from of the to a Oxysterols are more than in at least in has to of the of their in of oxysterols is a of their ability to at a of and their translocation between lipophilic of between lipophilic from erythrocytes to is and have the of the of of between human erythrocytes and the of between erythrocytes and in of erythrocytes The rate from red cells to a of lipophilic was to be a of similar the of 25-hydroxycholesterol from erythrocytes to plasma was found to occur times faster than of cholesterol, was possible to the of exchange of 25-hydroxycholesterol from the plasma to the in the of between and was of membranes and the in the rate the of was to be times of and and a properties of on and between properties of the and effects of the hydroxyl group on the properties and of the oxysterols a between the properties of oxysterols in the the the rate of of oxysterols from a to a the rate of 25-hydroxycholesterol and the the was a between the of translocation of of was the oxysterols in human are and is in the is to the of more than cholesterol. 27-hydroxycholesterol is in on in is to the plasma and the The ability to between in to their oxysterols to of in of has been plasma of in of is the and in the of have the plasma of and have been reported to be of the and to be of in and of the oxysterols a the on 27-hydroxycholesterol is group 27-hydroxycholesterol is in are the properties of the oxysterols the we the between the of hydroxyl group and on the of the to human effects on the rate of of oxysterols between lipophilic and the in of and 25-hydroxycholesterol from the the to a of and the in the a of and of the of the of and a of and and 27-hydroxycholesterol of in to and are of in of 27-hydroxycholesterol in human and of and and 27-hydroxycholesterol in human of and a of of in the of and was from and of of of oxysterols between erythrocytes and plasma was of 25-hydroxycholesterol from the plasma to the in erythrocytes blood three times in and the One of was in of and of and of was on the cells of cells on the of was to the of the blood of exchange was from blood at was at at The of the plasma to of the was and of erythrocytes to of a of plasma and to was to the and the erythrocytes at in a of the of and a the of erythrocytes and The was the of the was and the of the erythrocytes was of the 27-hydroxycholesterol in in cholesterol, was in human and and to a of to a of the in more than was of at least between the blood and the was in of in in human of and a of of in the of the of plasma was the in of plasma from was in be the the oxysterols have been of in in human of and a of of in the The in was to the of the oxysterols and the of the was of in human plasma was The was a to and The and on human the of from erythrocytes to the of oxysterols was found to occur at a much rate than cholesterol. The three oxysterols at a rate than the oxysterols in the The rate of translocation of to be than of be the the the of the was possible to of is a of of has been in the of the relative of the of of between human erythrocytes and of membranes and has been to be between and the of of between human erythrocytes and of membranes and of from between to the the of we a in the we the plasma the and measured the rate of of the in was possible to the of of from to The between the oxysterols to the of the to rate of translocation of be be the the of the the of at a rate than cholesterol, of the was than cholesterol. the of in was of was at at a to the of of between human erythrocytes and a to was a similar of was the of the of in the of the the of the of and was of the of of of and 27-hydroxycholesterol a to least oxysterols in of the The of 27-hydroxycholesterol was of plasma 27-hydroxycholesterol was in the is in the the of 27-hydroxycholesterol in plasma is at least than the major oxysterols in human from of a to the of 27-hydroxycholesterol of and are in of the the of of in human of and a of of in the and of in of was in of the the the The of the plasma is in the of a in plasma the of of and of a of in a to is the and are The the in the of plasma of the and are of and The of is between of and cholesterol, the of a the to cholesterol, are to and are in a the of between lipophilic was at the of the a of the of of between human erythrocytes and of membranes and between to the of was found to be the The of the is in in the of the The of cells and plasma a of the the the of the of the a more of the are the properties of oxysterols has been the of The of are in the of the of oxysterols in the is a is such the group the the of the to the of the in the between the of the and the of the to the of the hydroxyl group to a the of oxysterols in The of hydroxyl group the to of the The are the hydroxyl and the are in to the The of is is a to from the the of the of additional the to a of the in a of the is the group of to the of the the of the and the of on a of of a and the of the the of at in to properties similar to the of the is to of from on has been be a of 25-hydroxycholesterol between the and of the a of the and a of the properties of on and between a from the and the high rate of translocation of biological to the rate of of a be in the distance between the and the hydroxyl group is the greatest in the rate of of and 27-hydroxycholesterol from erythrocytes to plasma was found to be than of of the oxysterols of the is hydroxyl in the have effects on and on has been reported to be between a and at a rate than of 25-hydroxycholesterol properties of on and between in was in The rate of of was found to be than the rate of of the three but than the rate of of cholesterol. be the and in the rate of translocation of was similar to of in the in the rate of translocation of and in in is to be of the in of to the of the to the the rate of translocation between be a critical is the of a is a in the and to in is of the and The is a the is a of in the of in are the of the of be to be similar to of cholesterol. the of oxysterols in is similar to of plasma of in of of oxysterols in the human to the translocation of a of the occur to be the of more of the the oxysterols a to the the of and 27-hydroxycholesterol, be and of the be in the of of the in of the oxysterols is to be the critical the The rate of translocation of the oxysterols biological membranes be of and oxysterols rate is to be a of the the is a between the rate of translocation of in biological membranes and the rate of their oxysterols are and are of of of and 25-hydroxycholesterol is a more of in cells than of The properties of oxysterols be to their be has are to the of the has a and high and 27-hydroxycholesterol of 27-hydroxycholesterol in human of 25-hydroxycholesterol in the is from a the of and and 27-hydroxycholesterol and of a of The has been of the major biological of be to and 27-hydroxycholesterol of is to is the of the additional in is of critical rate of translocation between lipophilic from the of the on the oxysterols is a between rate of translocation in and the of the in is a between translocation and the ability of to Oxysterols are of have been in of of and One of their and is in of of from of the to a Oxysterols are more than in at least in has to of the of their in The of oxysterols is a of their ability to at a of and their translocation between lipophilic The of between lipophilic from erythrocytes to is and have the of the of of between human erythrocytes and the of between erythrocytes and in of erythrocytes The rate from red cells to a of lipophilic was to be a of similar the of 25-hydroxycholesterol from erythrocytes to plasma was found to occur times faster than of cholesterol, was possible to the of exchange of 25-hydroxycholesterol from the plasma to the in the of between and was of membranes and the in the rate the of was to be times of and and a properties of on and between properties of the and effects of the hydroxyl group on the properties and of the oxysterols a between the properties of oxysterols in the the the rate of of oxysterols from a to a the rate of 25-hydroxycholesterol and the the was a between the of translocation of of was the oxysterols in human are and is in the is to the of more than cholesterol. 27-hydroxycholesterol is in on in is to the plasma and the The ability to between in to their oxysterols to of cholesterol. The in of has been plasma of in of is the and in the of have the plasma of 4β-hydroxycholesterol. and have been reported to be of the and to be of in and of the oxysterols a the on 27-hydroxycholesterol is group 27-hydroxycholesterol is in are the properties of the oxysterols the we the between the of hydroxyl group and on the of the to human effects on the rate of of oxysterols between lipophilic and the in of and 25-hydroxycholesterol from the the to a of and the in the a of and of the of the of and a of and and 27-hydroxycholesterol of in to and are of in of 27-hydroxycholesterol in human and of and and 27-hydroxycholesterol in human of and a of of in the of and was from and of of of oxysterols between erythrocytes and plasma was of 25-hydroxycholesterol from the plasma to the in erythrocytes blood three times in and the One of was in of and of and of was on the cells of cells on the of was to the of the blood of exchange was from blood at was at at The of the plasma to of the was and of erythrocytes to of a of plasma and to was to the and the erythrocytes at in a of the of and a the of erythrocytes and The was the of the was and the of the erythrocytes was of the 27-hydroxycholesterol in in cholesterol, was in human and and to a of to a of the in more than was of at least between the blood and the was in of in in human of and a of of in the of the of plasma was the in of plasma from was in be the the oxysterols have been of in in human of and a of of in the The in was to the of the oxysterols and the of the was of in human plasma was The was a to and The and on human the and 25-hydroxycholesterol from the the to a of and the in the a of and of the of the of and a of and and 27-hydroxycholesterol of in to and are of in of 27-hydroxycholesterol in human and of and and 27-hydroxycholesterol in human of and a of of in the of and was from and of and 25-hydroxycholesterol from the the to a of and the in the a of and of the of the of and a of and and 27-hydroxycholesterol of in to and are of in of 27-hydroxycholesterol in human and of and and 27-hydroxycholesterol in human of and a of of in the of and was from and of of of oxysterols between erythrocytes and plasma was of 25-hydroxycholesterol from the plasma to the in erythrocytes blood three times in and the One of was in of and of and of was on the cells of cells on the of was to the of the blood The of oxysterols between erythrocytes and plasma was of 25-hydroxycholesterol from the plasma to the in erythrocytes blood three times in and the One of was in of and of and of was on the cells of cells on the of was to the of the blood of exchange was from blood at was at at The of the plasma to of the was and was from blood at was at at The of the plasma to of the was and of erythrocytes to of a of plasma and to was to the and the erythrocytes at in a of the of and a the of erythrocytes and The was the of the was and the of the erythrocytes was of erythrocytes to of a of plasma and to was to the and the erythrocytes at in a of the of and a the of erythrocytes and The was the of the was and the of the erythrocytes was of the 27-hydroxycholesterol in in cholesterol, was in human and and to a of to a of the in more than was of at least between the blood and the was in of in in human of and a of of in the of the of plasma was the in of plasma from was in be the the oxysterols have been of in in human of and a of of in the The in was to the of the oxysterols and the of the was of the 27-hydroxycholesterol in in cholesterol, was in human and and to a of to a of the in more than was of at least between the blood and the was in of in in human of and a of of in the of the of plasma was the in of plasma from was in be the the oxysterols have been of in in human of and a of of in the The in was to the of the oxysterols and the of the was of in human plasma was The was a to and The and Oxysterols of in human plasma was The was a to and The and on human the on human the of from erythrocytes to the of oxysterols was found to occur at a much rate than cholesterol. The three oxysterols at a rate than the oxysterols in the The rate of translocation of to be than of be the the the of the was possible to of is a of of has been in the of the relative of the of of between human erythrocytes and of membranes and has been to be between and the of of between human erythrocytes and of membranes and of from between to the the of we a in the we the plasma the and measured the rate of of the in was possible to the of of from to The between the oxysterols to the of the to rate of translocation of be be the the of the the of at a rate than cholesterol, of the was than cholesterol. the of in was of was at at a to the of of between human erythrocytes and a to was a similar of was the of the of in the of the the of the of and was of the of of of and 27-hydroxycholesterol a to least oxysterols in of the The of 27-hydroxycholesterol was of plasma 27-hydroxycholesterol was in the is in the the of 27-hydroxycholesterol in plasma is at least than the major oxysterols in human from of a to the of 27-hydroxycholesterol of and are in of the the of of in human of and a of of in the and of in of was in of the the the The of the plasma is in the of a in plasma the of of and The of is between of and cholesterol, the of Transfer of from erythrocytes to the of oxysterols was found to occur at a much rate than cholesterol. The three oxysterols at a rate than the oxysterols in the The rate of translocation of to be than of be the the the of the was possible to of is a of of has been in the of the relative of the of of between human erythrocytes and of membranes and has been to be between and the of of between human erythrocytes and of membranes and of from between to the the of we a in the we the plasma the and measured the rate of of the in was possible to the of of from to The between the oxysterols to the of the to rate of translocation of be be the the of the the of at a rate than cholesterol, of the was than cholesterol. the of in was of was at at a to the of of between human erythrocytes and a to was a similar of was the of the of in the of the the of the of and was the of oxysterols was found to occur at a much rate than cholesterol. The three oxysterols at a rate than the oxysterols in the The rate of translocation of to be than of cholesterol. be the the the of the was possible to of is a of of has been in the of the relative of the of of between human erythrocytes and of membranes and has been to be between and the of of between human erythrocytes and of membranes and of from between to the the of we a in the we the plasma the and measured the rate of of the in was possible to the of of from to The between the oxysterols to the of the to rate of translocation of be be the the of the the of at a rate than cholesterol, of the was than cholesterol. the of in was of was at at a to the of of between human erythrocytes and a to was a similar of was the of the of in the of the the of the of and was of the of of of and 27-hydroxycholesterol a to least oxysterols in of the The of 27-hydroxycholesterol was of plasma 27-hydroxycholesterol was in the is in the the of 27-hydroxycholesterol in plasma is at least than the major oxysterols in human from of a to the of 27-hydroxycholesterol of and are in of the the of of in human of and a of of in the and of in of was in of the the the The of the plasma is in the of a in plasma the of the of of of and 27-hydroxycholesterol a to least oxysterols in of the The of 27-hydroxycholesterol was of plasma 27-hydroxycholesterol was in the is in the the of 27-hydroxycholesterol in plasma is at least than the major oxysterols in human from of a to the of 27-hydroxycholesterol The of and are in of the the of of in human of and a of of in the and of in of was in of the the the The of the plasma is in the of a in plasma the of a the to cholesterol, are to and are in a the of between lipophilic was at the of the a of the of of between human erythrocytes and of membranes and between to the of was found to be the The of the is in in the of the The of cells and plasma a of the the the of the of the a more of the are the properties of oxysterols has been the of The of are in the of the of oxysterols in the is a is such the group the the of the to the of the in the between the of the and the of the to the of the hydroxyl group to a the of the of additional the to a of the in a of the is the group of to the of the the of the and the of on a of of a and the of the the of at in to properties similar to the of the is to of from on has been be a of 25-hydroxycholesterol between the and of the a of the and a of the properties of on and between a from the and the high rate of translocation of biological to the rate of of a be in the distance between the and the hydroxyl group is the greatest in the rate of of and 27-hydroxycholesterol from erythrocytes to plasma was found to be than of of the oxysterols of the is hydroxyl in the have effects on and on has been reported to be between a and at a rate than of 25-hydroxycholesterol properties of on and between in was in The rate of of was found to be than the rate of of the three but than the rate of of cholesterol. be the and in the rate of translocation of was similar to of in the in the rate of translocation of and in in is to be of the in of to the of the to the the rate of translocation between be a critical is the of a is a in the and to in is of the and The is a the is a of in the of in are the of the of be to be similar to of cholesterol. the of oxysterols in is similar to of plasma of in of of oxysterols in the human to the translocation of a of the occur to be the of more of the the oxysterols a to the the of and 27-hydroxycholesterol, be and of the be in the of of the in of the oxysterols is to be the critical the The rate of translocation of the oxysterols biological membranes be of and oxysterols rate is to be a of the the is a between the rate of translocation of in biological membranes and the rate of their oxysterols are and are of of of and 25-hydroxycholesterol is a more of in cells than of The properties of oxysterols be to their be has are to the of the has a and high and 27-hydroxycholesterol of 27-hydroxycholesterol in human of 25-hydroxycholesterol in the is from a the of and and 27-hydroxycholesterol and of a of The has been of the major biological of be to and 27-hydroxycholesterol of is to is the of the additional in is of critical rate of translocation between lipophilic from the of the on the oxysterols is a between rate of translocation in and the of the in is a between translocation and the ability of to a the to cholesterol, are to and are in a the of between lipophilic was at the of the a of the of of between human erythrocytes and of membranes and between to the of was found to be the The of the is in in the of the The of cells and plasma a of the the the of the of the a more of the are the properties of oxysterols has been the of The of are in the of the of oxysterols in the is a is such the group the the of the to the of the in the between the of the and the of the to the of the hydroxyl group to a the of the of additional the to a of the in a of the is the group of to the of the the of the and the of on a of of a and the of the the of at in to properties similar to the of the is to of from on has been be a of 25-hydroxycholesterol between the and of the a of the and a of the properties of on and between a from the and the high rate of translocation of biological to the rate of of a be in the distance between the and the hydroxyl group is the greatest in the rate of of and 27-hydroxycholesterol from erythrocytes to plasma was found to be than of of the oxysterols of the is hydroxyl in the have effects on and on has been reported to be between a and at a rate than of 25-hydroxycholesterol properties of on and between in was in The rate of of was found to be than the rate of of the three but than the rate of of cholesterol. be the and in the rate of translocation of was similar to of in the The in the rate of translocation of and in in is to be of the in of to the of the to the the rate of translocation between be a critical is the of a is a in the and to in is of the and The is a the is a of in the of in are the of the The of be to be similar to of cholesterol. the of oxysterols in is similar to of plasma of in of of oxysterols in the human to the translocation of a of the occur to be the of more of the the oxysterols a to the the of and 27-hydroxycholesterol, be and of the be in the of The of the in of the oxysterols is to be the critical the The rate of translocation of the oxysterols biological membranes be of and oxysterols rate is to be a of the the is a between the rate of translocation of in biological membranes and the rate of their oxysterols are and are of of of and 25-hydroxycholesterol is a more of in cells than of The properties of oxysterols be to their be has are to the of the has a and high and 27-hydroxycholesterol of 27-hydroxycholesterol in human of 25-hydroxycholesterol in the is from a the of and and 27-hydroxycholesterol and of a of The has been of the major biological of be to and 27-hydroxycholesterol of is to is the of the additional in is of critical rate of translocation between lipophilic from the of the on the oxysterols is a between rate of translocation in and the of the in is a between translocation and the ability of to The of is are to has been from the and the