β-Carotene, the most abundant provitamin A carotenoid in the diet, is converted to retinal by β-carotene 15,15'-monoxygenase (BCMO1). However, β-carotene absorption and conversion into retinal is extremely variable among individuals, with proportions of low responders to dietary β-carotene as high as 45%. Recently, 2 common nonsynonymous single nucleotide polymorphisms (SNPs) within the BCMO1 coding region (R267S; rs12934922 and A379V; rs7501331) revealed reduced catalytic activity, confirming that genetic variations contribute to the low responder phenotype. Because 4 SNPs 5' upstream from the BCMO1 gene were recently shown to affect circulating carotenoid concentrations, the current study aimed to investigate the effects of these SNPs on β-carotene conversion efficiency. Three of the 4 polymorphisms (rs6420424, rs11645428, and rs6564851) reduced the catalytic activity of BCMO1 in female volunteers by 59, 51, and 48%, respectively. The TG-rich lipoprotein fraction retinyl palmitate:β-carotene ratio was negatively correlated with the G allele of rs11645428 (r = -0.44; P = 0.018), whereas it was positively correlated with the G allele of rs6420424 (r = 0.53; P = 0.004) and the T allele of rs6564851 (r = 0.41; P = 0.028). Furthermore, large inter-ethnic variations in frequency of affected alleles were detected, with frequencies varying from 43 to 84% (rs6420424), 52 to 100% (rs11645428), and 19 to 67% (rs6564851). In summary, a range of SNPs can influence the effectiveness of using plant-based provitamin A carotenoids to increase vitamin A status in at-risk population groups and this effect may vary depending on ethnic origin.
In humans, varying amounts of absorbed β-carotene are oxidatively cleaved by the enzyme β,β-carotene 15,15'-monooxygenase 1 (BCMO1) into two molecules of all-trans-retinal. The other carotenoid cleavage enzyme β,β-carotene 9',10'-dioxygenase (BCDO2) cleaves β-carotene at the 9',10' double bond forming β-apo-10'-carotenal and β-ionone. Although the contribution of BCDO2 to vitamin A formation has long been debated, BCMO1 is currently considered the key enzyme for retinoid metabolism. Furthermore, BCMO1 has limited enzyme activity towards carotenoids other than provitamin A carotenoids, whereas BCDO2 exhibits a broader specificity. Both enzymes are located at different sites within the cell, with BCMO1 being a cytosolic protein and BCDO2 being located in the mitochondria. Expression of BCMO1 in tissues other than the intestine has recently revealed its function for tissue-specific retinoid metabolism with importance in embryogenesis and lipid metabolism. On the other hand, biological activity of BCDO2 metabolites has been shown to be important in protecting against carotenoid-induced mitochondrial dysfunction. Single-nucleotide polymorphisms (SNPs) such as R267S and A379V in BCMO1 can partly explain inter-individual variations observed in carotenoid metabolism. Advancing knowledge about the physiological role of these two enzymes will contribute to understanding the importance of carotenoids in health and disease.
Havforskningsinstituttets institusjonelle arkiv Brage IMR - Institutional repository of the Institute of Marine Research b r a g e i m rDette er forfatters siste versjon av den fagfellevurderte artikkelen, vanligvis omtalt som postprint. I Brage IMR er denne artikkelen ikke publisert med forlagets layout fordi forlaget ikke tillater dette. Du finner lenke til forlagets versjon i Brage-posten. Det anbefales at referanser til artikkelen hentes fra forlagets side. Ved lenking til artikkelen skal det lenkes til post i Brage IMR, ikke direkte til pdf-fil.This is the author's last version of the article after peer review and is not the publisher's version, usually referred to as postprint. You will find a link to the publisher's version in Brage IMR. It is recommended that you obtain the references from the publisher's site.Linking to the article should be to the Brage-record, not lear vacuoles and goblet cell hypertrophy and hyperplasia (4 -8) . 39Furthermore, substituting vegetable oils (VO) for fish oil (FO) 40 ingredients naturally decreases the high n-3:n-6 PUFA ratio of 41 a carnivorous fish's evolutionary consistent diet (9) . Alteration 42 of the dietary n-3:n-6 PUFA ratio can subsequently affect 43 the production of potent bioactive lipidic mediators of inflam-44 mation, termed as 'eicosanoids', which are synthesised from 45 C20 PUFA in cellular membranes (10) . 46In opposition to mammals, EPA (20 : 5n-3) predominates . Abbreviations: AA, arachidonic acid; ANF, anti-nutritional factor; COX-2, cyclo-oxygenase-2; cPLA 2 , cytosolic phospholipase A 2 ; DGLA, dihomo-g-linolenic acid; FM, fishmeal; FMFO, control diet of 100 % FM and 100 % fish oil; FO, fish oil; PLA 2 , phospholipase A 2 ; PP, plant protein; Tris, 2-amino-2-hydroxymethylpropane-1,3-diol; VO, vegetable oil; 40PP70VO, 40 % PP and 70 % VO replacement in diet; 80PP35VO, 80 % PP and 35 % VO replacement in diet; 80PP70VO, 80 % PP and 70 % VO replacement in diet.
Background: Retinol isotope dilution (RID) is used to determine vitamin A total body stores (TBS) after an oral dose of a vitamin A stable isotope. The generally accepted prediction equation proposed by Olson’s group in 1989 (Furr et al. Am J Clin Nutr 1989;49:713–6) includes factors related to dose absorption and retention, isotope equilibration in plasma compared with stores, catabolism during the mixing period, and the optimal time for measuring plasma isotope enrichment.Objectives: The objectives were 1) to develop a modified RID equation and identify an earlier sampling time for predicting TBS and 2) to improve prediction in individuals as well as groups.Methods: To develop a modified RID equation, we used results of model-based compartmental analysis [the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org)] of plasma [13C10]retinol kinetic data from 32 previously studied, healthy young adults of European ancestry who had moderate vitamin A intakes and who ingested 2.95 μmol [13C10]retinyl acetate.Results: We examined the time dependence of factors in the prediction equation related to absorption/retention (Fa) and isotope equilibration (S) and determined that 4 or 5 d postdosing was the optimal sampling time. TBS calculated by the equation TBS = Fa x S x (1/SAp), where SAp is plasma retinol specific activity (fraction of dose/μmol), were highly correlated with model-predicted TBS (r = 0.95 and 0.96 for 4 and 5 d, respectively; P < 0.001); predictions for individuals were also highly correlated (Rs = 0.94 and 0.94; P < 0.001).Conclusion: The equation TBS ≈ 0.5 × (1/SAp) accurately predicted vitamin A TBS in this group of 32 healthy young adults and its individual members with the use of data from 1 blood sample taken 4 d after isotope administration.
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