Common Variants of Cytochrome P450 4F2 Exhibit Altered Vitamin E-?-Hydroxylase Specific Activity  

Oleh:

Bardowell, Sabrina A. ; Ste, David E. ; Parker, Robert S.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 140 no. 11 (Nov. 2010), page 1901-1906 .
Topik: Vitamin E

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2010.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Human cytochrome P450 4F2 (CYP4F2) catalyzes the ?-hydroxylation of the side chain of tocopherols (TOH) and tocotrienols (T3), the first step in their catabolism to polar metabolites excreted in urine. CYP4F2, in conjunction with a-TOH transfer protein, results in the conserved phenotype of selective retention of a-TOH. The purpose of this work was to determine the functional consequences of 2 common genetic variants in the human CYP4F2 gene on vitamin E-?-hydroxylase specific activity using the 6 major dietary TOH and T3 as substrate. CYP4F2-mediated ?-hydroxylase specific activity was measured in microsomal preparations from insect cells that express wild-type or polymorphic variants of the human CYP4F2 protein. The W12G variant exhibited a greater enzyme specific activity (pmol product · min-1 · pmol CYP4F2-1) compared with wild-type enzyme for both TOH and T3, 230–275% of wild-type toward a, ?, and d-TOH and 350% of wild-type toward a, ?, and d-T3. In contrast, the V433M variant had lower enzyme specific activity toward TOH (42–66% of wild type) but was without a significant effect on the metabolism of T3. Because CYP4F2 is the only enzyme currently shown to metabolize vitamin E in humans, the observed substrate-dependent alterations in enzyme activity associated with these genetic variants may result in alterations in vitamin E status in individuals carrying these mutations and constitute a source of variability in vitamin E status.

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