Common variants of cytochrome P450 4F2 exhibit altered vitamin E-{omega}-hydroxylase specific activity.
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Bardowell SA, Stec DE, Parker RS
Common variants of cytochrome P450 4F2 exhibit altered vitamin E-{omega}-hydroxylase specific activity.
J Nutr. 2010 Nov;140(11):1901-6. doi: 10.3945/jn.110.128579. Epub 2010 Sep 22.
- PubMed ID
- 20861217 [ View in PubMed]
- Abstract
Human cytochrome P450 4F2 (CYP4F2) catalyzes the omega-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 alpha-TOH transfer protein, results in the conserved phenotype of selective retention of alpha-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-omega-hydroxylase specific activity using the 6 major dietary TOH and T3 as substrate. CYP4F2-mediated omega-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 alpha, gamma, and delta-TOH and 350% of wild-type toward alpha, gamma, and delta-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.