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Kevin Carpenter - One of the best experts on this subject based on the ideXlab platform.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Keow G Sim, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, William J Rhead, Gregory PetersAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, Gladys Ho, William J RheadAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans. © 2010 Wiley-Liss, Inc.
Yoshie Kitamura - One of the best experts on this subject based on the ideXlab platform.
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increased de novo Riboflavin synthesis and hydrolysis of fmn are involved in Riboflavin secretion from hyoscyamus albus hairy roots under iron deficiency
Plant Physiology and Biochemistry, 2012Co-Authors: Ataru Higa, Jebunnahar Khandakar, Yuko Mori, Yoshie KitamuraAbstract:Abstract Riboflavin secretion by Hyoscyamus albus hairy roots under Fe deficiency was examined to determine where Riboflavin is produced and whether production occurs via an enhancement of Riboflavin biosynthesis or a stimulation of flavin mononucleotide (FMN) hydrolysis. Confocal fluorescent microscopy showed that Riboflavin was mainly localized in the epidermis and cortex of the root tip and, at the cellular level, in the apoplast. The expressions of three genes involved in the de novo biosynthesis of Riboflavin ( GTP cyclohydrolase II/3,4- dihydroxy -2- butanone 4- phosphate synthase ; 6,7- dimethyl -8- ribityllumazine synthase ; Riboflavin synthase ) were compared between Fe-starved and Fe-replete roots over a time-course of 7 days, using RT-PCR. All three genes were found to be highly expressed over the period 1–7 days in the roots cultured under Fe deficiency. Since Riboflavin secretion began to be detected only from 3 days, there was a lag phase observed between the increased transcript accumulations and Riboflavin secretion. To determine whether FMN hydrolysis might contribute to the Riboflavin secretion in Fe-deficient root cultures, FMN hydrolase activity was determined and was found to be substantially increased after 3 days, when Riboflavin secretion became detectable. These results suggested that not only de novo Riboflavin synthesis but also the hydrolysis of FMN contributes to Riboflavin secretion under conditions of Fe deficiency. Respiration activity was assayed during the time-course, and was also found to be enhanced after 3 days under Fe deficiency, suggesting a possible link with Riboflavin secretion. On the other hand, several respiratory inhibitors were found not to affect Riboflavin synthase transcript accumulation.
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root tip dependent active Riboflavin secretion by hyoscyamus albus hairy roots under iron deficiency
Plant Physiology and Biochemistry, 2008Co-Authors: Ataru Higa, Erika Miyamoto, Laiq Ur Rahman, Yoshie KitamuraAbstract:Hyoscyamus albus hairy roots with/without an exogenous gene (11 clones) were established by inoculation of Agrobacterium rhizogenes. All clones cultured under iron-deficient condition secreted Riboflavin from the root tips into the culture medium and the productivity depended on the number and size of root tips among the clones. A decline of pH was observed before Riboflavin production and root development. By studying effects of proton-pump inhibitors, medium acidification with external organic acid, and Riboflavin addition upon pH change and Riboflavin productivity, we indicate that Riboflavin efflux is not directly connected to active pH reduction, and more significantly active Riboflavin secretion occurs as a response to an internal requirement in H. albus hairy roots under iron deficiency.
William J Rhead - One of the best experts on this subject based on the ideXlab platform.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Keow G Sim, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, William J Rhead, Gregory PetersAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, Gladys Ho, William J RheadAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans. © 2010 Wiley-Liss, Inc.
Gladys Ho - One of the best experts on this subject based on the ideXlab platform.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, Gladys Ho, William J RheadAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans. © 2010 Wiley-Liss, Inc.
Atsushi Yonezawa - One of the best experts on this subject based on the ideXlab platform.
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Riboflavin Transporters RFVT/SLC52A Mediate Translocation of Riboflavin, Rather than FMN or FAD, across Plasma Membrane
Biological & Pharmaceutical Bulletin, 2017Co-Authors: Congyun Jin, Atsushi Yonezawa, Yoshiaki Yao, Hiroki Yoshimatsu, Tomohiro Omura, Satoshi Imai, Yuki Otani, Shunsaku Nakagawa, Takayuki Nakagawa, Kazuo MatsubaraAbstract:Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from Riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to Riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular Riboflavin concentrations. The uptake of Riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that Riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in Riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by Riboflavin kinase and FAD synthase.
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Involvement of Riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of Riboflavin in mice.
European Journal of Pharmacology, 2013Co-Authors: Yoshiaki Yao, Atsushi Yonezawa, Satohiro Masuda, Hiroki Yoshimatsu, Tomohiro Omura, Kazuo MatsubaraAbstract:Abstract Riboflavin (vitamin B2) acts as an intermediary during various biochemical oxidation–reduction reactions in the liver. Hepatic Riboflavin homeostasis is suggested to be maintained through its transporter(s). Riboflavin transporters, RFVT2/Slc52a2 and RFVT3/Slc52a3, have been identified in rodents. However, the role of each RFVT in the hepatic homeostasis of Riboflavin has not yet been fully clarified. In this study, we assessed the contribution of each RFVT to Riboflavin uptake into the liver using in vitro and in vivo studies. The uptake of Riboflavin by mouse primary hepatocytes increased in a time-dependent and a concentration-dependent manner. Riboflavin transport was independent of extracellular Na+. However, the uptake decreased slightly along with the extracellular pH increases. Real-time PCR analysis revealed that the mRNA level of Slc52a2, or coding for mouse (m)RFVT2, in the mouse liver was 10 times higher than that of Slc52a3 (coding for mRFVT3). The uptake of Riboflavin at pH 7.4 by primary hepatocytes was significantly decreased by the transfection of Slc52a2-small interfering RNA (siRNA), but not Slc52a3-siRNA. Furthermore, we also confirmed the contribution of Riboflavin transporters in vivo. The Riboflavin concentrations in plasma, but not in the liver, were significantly decreased in mice fed on a Riboflavin-deficient diet for 8 weeks. The expression of Slc52a2 mRNA was significantly upregulated by Riboflavin deprivation. These results strongly suggest that mRFVT2 was involved in hepatic Riboflavin homeostasis.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Keow G Sim, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, William J Rhead, Gregory PetersAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans.
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maternal Riboflavin deficiency resulting in transient neonatal onset glutaric aciduria type 2 is caused by a microdeletion in the Riboflavin transporter gene gpr172b
Human Mutation, 2011Co-Authors: Atsushi Yonezawa, Satohiro Masuda, Kenichi Inui, Kevin Carpenter, Rikke K J Olsen, John J Mitchell, Gladys Ho, William J RheadAbstract:Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by Riboflavin supplementation. The mother was then found to be persistently Riboflavin deficient, suggesting that a possible genetic defect in Riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified Riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and Riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that Riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this Riboflavin transporter causes mild Riboflavin deficiency, and when coupled with nutritional Riboflavin deficiency in pregnancy, resulted in the transient Riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in Riboflavin transport in humans. © 2010 Wiley-Liss, Inc.