Incorporation of deuterated RRR- or all-rac-alpha-tocopherol in plasma and tissues of alpha-tocopherol transfer protein--null mice.
BACKGROUND
Most vitamin E supplements contain synthetic all-rac-alpha-tocopherol [2,5,7,8-tetramethyl-2RS-(4'RS,8'RS,12-trimethyltridecyl)-6-chromanol] with 8 stereoisomers; only 1 is identical to the natural stereoisomer, RRR-alpha-tocopherol [2,5,7,8-tetramethyl-2R-(4'R,8'R,12-trimethyltridecyl)-6-chromanol]. In humans, 2R-alpha-tocopherol stereoisomers are preferentially maintained in the plasma, a function that has been attributed to hepatic alpha-tocopherol transfer protein (alpha-TTP), but this hypothesis has not been tested.


OBJECTIVE
We sought to determine the functions of alpha-TTP by comparing mice that express alpha-TTP with mice that are genetically unable to express alpha-TTP.


METHODS
Adult alpha-TTP null (Ttpa(-/-); n = 5), heterozygous (Ttpa(+/-); n = 7), and wild-type (Ttpa(+/+); n = 3) mice consumed equimolar RRR-alpha-[5,7-(C(2)H(3))(2)]-(d(6))- and all-rac-alpha-[5-(C(2)H(3))]-(d(3))-tocopheryl acetates (30 mg/kg diet each) for 3 mo. Subsequently, we measured labeled and unlabeled alpha-tocopherols in plasma and 17 tissues.


RESULTS
In all mice, plasma and tissue d(6)- + d(3)-alpha-tocopherols represented approximate 80-90% of total alpha-tocopherol. In the Ttpa(-/-) mice, low total alpha-tocopherol concentrations were found in plasma (5.4%) and most other tissues (2-20%), but liver concentrations were 39% of those of Ttpa(+/+) mice. Peripheral tissue ratios of d(6)- to d(3)-alpha-tocopherol were 1.1 plus minus 0.1 and 1.8 plus minus 0.2 in Ttpa(-/-) and Ttpa(+/+) mice, respectively (P < 0.0001), showing that alpha-TTP preferentially selects 2R-alpha-tocopherols for secretion into plasma. This 2:1 ratio does not support the currently defined international unit of 1.36:1 RRR-alpha-tocopherol to all-rac-alpha-tocopherol.


CONCLUSIONS
Deletion of the alpha-TTP gene in mice results in an accumulation of dietary alpha-tocopherol in the liver and depletion of peripheral tissue alpha-tocopherol.
Leonard
Scott W
SW
Linus Pauling Institute, Oregon State University, Corvallis, USA.
Terasawa
Yuko
Y
Farese
Robert V
RV
Traber
Maret G
MG
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003903:Deuterium; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013237:Stereoisomerism; D014018:Tissue Distribution; D014811:Vitamin E Deficiency / Q000235:genetics* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000097:blood / Q000737:chemistry / Q000378:metabolism*
D000975:Antioxidants; D003903:Deuterium; D024502:alpha-Tocopherol