gene encoding -carotene 15,15 -monoxygenase alter. -carotene metabolism ...... sion of beta-carotene 15,15-mono-oxygenase in human tissues. J. Histochem.
The FASEB Journal • Research Communication
Two common single nucleotide polymorphisms in the gene encoding -carotene 15,15ⴕ-monoxygenase alter -carotene metabolism in female volunteers W. C. Leung,*,1 S. Hessel,*,§,1 C. Me´plan,*,† J. Flint,† V. Oberhauser,§ F. Tourniaire,*,‡ J. E. Hesketh,*,† J. von Lintig,§,储 and G. Lietz*,‡,2 *Human Nutrition Research Centre, †Institute of Cell and Molecular Biosciences, and ‡School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, UK; § Institute of Biology I, Animal Physiology and Neurobiology, Freiburg, Germany; and 储Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA The key enzyme responsible for -carotene conversion into retinal is -carotene 15,15ⴕ-monoxygenase (BCMO1). Since it has been reported that the conversion of -carotene into vitamin A is highly variable in up to 45% of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24%, respectively. In vitro biochemical characterization of the recombinant 267S ⴙ 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57% (P
