Selective accumulation of α-tocopherol in Drosophila is associated with cytochrome P450 tocopherol-ω-hydroxylase activity but not α-tocopherol transfer protein

Humans and other mammals actively discriminate among the various forms of vitamin E to selectively retain α-tocopherol, but the phylogenetic breadth of this trait is unknown. We sought to determine if the fruit fly, Drosophila melanogaster, similarly discriminates and if so by what mechanism. Larvae and adult flies fed diets containing predominantly γ- and δ-tocopherols were enriched in α-tocopherol. Inclusion in the diet of piperonyl butoxide (PBO), an insect cytochrome P450 inhibitor and inhibitor of tocopherol-ω-hydroxylase activity, greatly elevated tissue levels of δ-tocopherol but not α-tocopherol. Drosophila microsomes exhibited tocopherol-ω-hydroxylase activity in the order of δ-T > γ-T ≫ α-T, a pattern consistent with the effect of PBO in vivo. To determine if selectivity involved α-tocopherol transfer protein (α-TTP), adult flies were fed an equimolar mixture of d3-RRR- and d6-all-racemic α-tocopherol. Flies exhibited a d3/d6 ratio of 1.03, demonstrating an inability to discriminate on the basis of phytyl tail stereochemistry, a hallmark of α-TTP activity. We conclude that Drosophila preferentially accumulates α-tocopherol via a mechanism involving cytochrome P450 tocopherol-ω-hydroxylase-mediated catabolism of other tocopherols, but not a mammalian-like α-TTP. The selective pressure favoring this trait and its remarkable conservation from insects to humans requires elucidation.