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Kimie Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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menadione vitamin k3 is a catabolic product of oral phylloquinone vitamin k1 in the intestine and a circulating precursor of tissue Menaquinone 4 vitamin k2 in rats
Journal of Biological Chemistry, 2013Co-Authors: Yoshihisa Hirota, Yoshitomo Suhara, Maya Kamao, Kimie Nakagawa, Naoko Tsugawa, Kiyoshi Tanaka, Yuri Uchino, Atsuko Takeuchi, Natsumi Sawada, Akimori WadaAbstract:Mice have the ability to convert dietary phylloquinone (vitamin K1) into Menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity for phylloquinone but a strong prenylation activity for menadione (vitamin K3), which has long been postulated as an intermediate in this conversion. Further evidence indicates that when intravenously administered in mice phylloquinone can enter into tissues but is not converted further to Menaquinone-4. These findings raise the question whether phylloquinone is absorbed and delivered to tissues in its original form and converted to Menaquinone-4 or whether it is converted to menadione in the intestine followed by delivery of menadione to tissues and subsequent conversion to Menaquinone-4. To answer this question, we conducted cannulation experiments using stable isotope tracer technology in rats. We confirmed that the second pathway is correct on the basis of structural assignments and measurements of phylloquinone-derived menadione using high resolution MS analysis and a bioassay using recombinant UBIAD1 protein. Furthermore, high resolution MS and 1H NMR analyses of the product generated from the incubation of menadione with recombinant UBIAD1 revealed that the hydroquinone, but not the quinone form of menadione, was an intermediate of the conversion. Taken together, these results provide unequivocal evidence that menadione is a catabolic product of oral phylloquinone and a major source of tissue Menaquinone-4.
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in vivo metabolism of vitamin k in relation to the conversion of vitamin k1 to mk 4
Clinical calcium, 2009Co-Authors: Toshio Okano, Kimie Nakagawa, Maya KamaoAbstract:Phylloquinone is a major form (>90%) of dietary vitamin K, but the form of vitamin K that exists at the highest concentrations in tissues of animals and humans is Menaquinone-4 (MK-4) . Despite this great difference, the origin of tissue MK-4 had not been clarified until recently. We demonstrated that deuterium-labeled phylloquinone was converted into deuterium-labeled MK-4 in mice and this conversion occurred following an oral or enteral administration, but not parenteral administration. By the oral route, the phylloquinone with the deuterium-labeled side chain (phytyl side-chain) was clearly converted into Menaquinone-4 with a non-deuterium-labeled side chain (geranylgeranyl side-chain), implying that phylloquinone was converted into Menaquinone-4 via integral side-chain removal. Our results suggest that cerebral Menaquinone-4 originates from phylloquinone intake and the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into Menaquinone-4 in the intestine or tissues.
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conversion of phylloquinone vitamin k1 into Menaquinone 4 vitamin k2 in mice two possible routes for Menaquinone 4 accumulation in cerebra of mice
Journal of Biological Chemistry, 2008Co-Authors: Toshio Okano, Yuka Shimomura, Makiko Yamane, Yoshitomo Suhara, Maya Kamao, Makiko Sugiura, Kimie NakagawaAbstract:There are two forms of naturally occurring vitamin K, phylloquinone and the Menaquinones. Phylloquinone (vitamin K1) is a major type (>90%) of dietary vitamin K, but its concentrations in animal tissues are remarkably low compared with those of the Menaquinones, especially Menaquinone-4 (vitamin K2), the major form (>90%) of vitamin K in tissues. Despite this great difference, the origin of tissue Menaquinone-4 has yet to be exclusively defined. It is postulated that phylloquinone is converted into Menaquinone-4 and accumulates in extrahepatic tissues. To clarify this, phylloquinone with a deuterium-labeled 2-methyl-1,4-naphthoquinone ring was given orally to mice, and cerebra were collected for D NMR and liquid chromatography-tandem mass spectrometry analyses. We identified the labeled Menaquinone-4 that was converted from the given phylloquinone, and this conversion occurred following an oral or enteral administration, but not parenteral or intracerebroventricular administration. By the oral route, the phylloquinone with the deuterium-labeled side chain in addition to the labeled 2-methyl-1,4-naphthoquinone was clearly converted into a labeled Menaquinone-4 with a non-deuterium-labeled side chain, implying that phylloquinone was converted into Menaquinone-4 via integral side-chain removal. The conversion also occurred in cerebral slice cultures and primary cultures. Deuterium-labeled menadione was consistently converted into the labeled Menaquinone-4 with all of the administration routes and the culture conditions tested. Our results suggest that cerebral Menaquinone-4 originates from phylloquinone intake and that there are two routes of accumulation, one is the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into Menaquinone-4 in tissues, and another is cleavage and prenylation within the cerebrum.
Yoshitomo Suhara - One of the best experts on this subject based on the ideXlab platform.
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menadione vitamin k3 is a catabolic product of oral phylloquinone vitamin k1 in the intestine and a circulating precursor of tissue Menaquinone 4 vitamin k2 in rats
Journal of Biological Chemistry, 2013Co-Authors: Yoshihisa Hirota, Yoshitomo Suhara, Maya Kamao, Kimie Nakagawa, Naoko Tsugawa, Kiyoshi Tanaka, Yuri Uchino, Atsuko Takeuchi, Natsumi Sawada, Akimori WadaAbstract:Mice have the ability to convert dietary phylloquinone (vitamin K1) into Menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity for phylloquinone but a strong prenylation activity for menadione (vitamin K3), which has long been postulated as an intermediate in this conversion. Further evidence indicates that when intravenously administered in mice phylloquinone can enter into tissues but is not converted further to Menaquinone-4. These findings raise the question whether phylloquinone is absorbed and delivered to tissues in its original form and converted to Menaquinone-4 or whether it is converted to menadione in the intestine followed by delivery of menadione to tissues and subsequent conversion to Menaquinone-4. To answer this question, we conducted cannulation experiments using stable isotope tracer technology in rats. We confirmed that the second pathway is correct on the basis of structural assignments and measurements of phylloquinone-derived menadione using high resolution MS analysis and a bioassay using recombinant UBIAD1 protein. Furthermore, high resolution MS and 1H NMR analyses of the product generated from the incubation of menadione with recombinant UBIAD1 revealed that the hydroquinone, but not the quinone form of menadione, was an intermediate of the conversion. Taken together, these results provide unequivocal evidence that menadione is a catabolic product of oral phylloquinone and a major source of tissue Menaquinone-4.
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conversion of phylloquinone vitamin k1 into Menaquinone 4 vitamin k2 in mice two possible routes for Menaquinone 4 accumulation in cerebra of mice
Journal of Biological Chemistry, 2008Co-Authors: Toshio Okano, Yuka Shimomura, Makiko Yamane, Yoshitomo Suhara, Maya Kamao, Makiko Sugiura, Kimie NakagawaAbstract:There are two forms of naturally occurring vitamin K, phylloquinone and the Menaquinones. Phylloquinone (vitamin K1) is a major type (>90%) of dietary vitamin K, but its concentrations in animal tissues are remarkably low compared with those of the Menaquinones, especially Menaquinone-4 (vitamin K2), the major form (>90%) of vitamin K in tissues. Despite this great difference, the origin of tissue Menaquinone-4 has yet to be exclusively defined. It is postulated that phylloquinone is converted into Menaquinone-4 and accumulates in extrahepatic tissues. To clarify this, phylloquinone with a deuterium-labeled 2-methyl-1,4-naphthoquinone ring was given orally to mice, and cerebra were collected for D NMR and liquid chromatography-tandem mass spectrometry analyses. We identified the labeled Menaquinone-4 that was converted from the given phylloquinone, and this conversion occurred following an oral or enteral administration, but not parenteral or intracerebroventricular administration. By the oral route, the phylloquinone with the deuterium-labeled side chain in addition to the labeled 2-methyl-1,4-naphthoquinone was clearly converted into a labeled Menaquinone-4 with a non-deuterium-labeled side chain, implying that phylloquinone was converted into Menaquinone-4 via integral side-chain removal. The conversion also occurred in cerebral slice cultures and primary cultures. Deuterium-labeled menadione was consistently converted into the labeled Menaquinone-4 with all of the administration routes and the culture conditions tested. Our results suggest that cerebral Menaquinone-4 originates from phylloquinone intake and that there are two routes of accumulation, one is the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into Menaquinone-4 in tissues, and another is cleavage and prenylation within the cerebrum.
Maya Kamao - One of the best experts on this subject based on the ideXlab platform.
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menadione vitamin k3 is a catabolic product of oral phylloquinone vitamin k1 in the intestine and a circulating precursor of tissue Menaquinone 4 vitamin k2 in rats
Journal of Biological Chemistry, 2013Co-Authors: Yoshihisa Hirota, Yoshitomo Suhara, Maya Kamao, Kimie Nakagawa, Naoko Tsugawa, Kiyoshi Tanaka, Yuri Uchino, Atsuko Takeuchi, Natsumi Sawada, Akimori WadaAbstract:Mice have the ability to convert dietary phylloquinone (vitamin K1) into Menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity for phylloquinone but a strong prenylation activity for menadione (vitamin K3), which has long been postulated as an intermediate in this conversion. Further evidence indicates that when intravenously administered in mice phylloquinone can enter into tissues but is not converted further to Menaquinone-4. These findings raise the question whether phylloquinone is absorbed and delivered to tissues in its original form and converted to Menaquinone-4 or whether it is converted to menadione in the intestine followed by delivery of menadione to tissues and subsequent conversion to Menaquinone-4. To answer this question, we conducted cannulation experiments using stable isotope tracer technology in rats. We confirmed that the second pathway is correct on the basis of structural assignments and measurements of phylloquinone-derived menadione using high resolution MS analysis and a bioassay using recombinant UBIAD1 protein. Furthermore, high resolution MS and 1H NMR analyses of the product generated from the incubation of menadione with recombinant UBIAD1 revealed that the hydroquinone, but not the quinone form of menadione, was an intermediate of the conversion. Taken together, these results provide unequivocal evidence that menadione is a catabolic product of oral phylloquinone and a major source of tissue Menaquinone-4.
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in vivo metabolism of vitamin k in relation to the conversion of vitamin k1 to mk 4
Clinical calcium, 2009Co-Authors: Toshio Okano, Kimie Nakagawa, Maya KamaoAbstract:Phylloquinone is a major form (>90%) of dietary vitamin K, but the form of vitamin K that exists at the highest concentrations in tissues of animals and humans is Menaquinone-4 (MK-4) . Despite this great difference, the origin of tissue MK-4 had not been clarified until recently. We demonstrated that deuterium-labeled phylloquinone was converted into deuterium-labeled MK-4 in mice and this conversion occurred following an oral or enteral administration, but not parenteral administration. By the oral route, the phylloquinone with the deuterium-labeled side chain (phytyl side-chain) was clearly converted into Menaquinone-4 with a non-deuterium-labeled side chain (geranylgeranyl side-chain), implying that phylloquinone was converted into Menaquinone-4 via integral side-chain removal. Our results suggest that cerebral Menaquinone-4 originates from phylloquinone intake and the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into Menaquinone-4 in the intestine or tissues.
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conversion of phylloquinone vitamin k1 into Menaquinone 4 vitamin k2 in mice two possible routes for Menaquinone 4 accumulation in cerebra of mice
Journal of Biological Chemistry, 2008Co-Authors: Toshio Okano, Yuka Shimomura, Makiko Yamane, Yoshitomo Suhara, Maya Kamao, Makiko Sugiura, Kimie NakagawaAbstract:There are two forms of naturally occurring vitamin K, phylloquinone and the Menaquinones. Phylloquinone (vitamin K1) is a major type (>90%) of dietary vitamin K, but its concentrations in animal tissues are remarkably low compared with those of the Menaquinones, especially Menaquinone-4 (vitamin K2), the major form (>90%) of vitamin K in tissues. Despite this great difference, the origin of tissue Menaquinone-4 has yet to be exclusively defined. It is postulated that phylloquinone is converted into Menaquinone-4 and accumulates in extrahepatic tissues. To clarify this, phylloquinone with a deuterium-labeled 2-methyl-1,4-naphthoquinone ring was given orally to mice, and cerebra were collected for D NMR and liquid chromatography-tandem mass spectrometry analyses. We identified the labeled Menaquinone-4 that was converted from the given phylloquinone, and this conversion occurred following an oral or enteral administration, but not parenteral or intracerebroventricular administration. By the oral route, the phylloquinone with the deuterium-labeled side chain in addition to the labeled 2-methyl-1,4-naphthoquinone was clearly converted into a labeled Menaquinone-4 with a non-deuterium-labeled side chain, implying that phylloquinone was converted into Menaquinone-4 via integral side-chain removal. The conversion also occurred in cerebral slice cultures and primary cultures. Deuterium-labeled menadione was consistently converted into the labeled Menaquinone-4 with all of the administration routes and the culture conditions tested. Our results suggest that cerebral Menaquinone-4 originates from phylloquinone intake and that there are two routes of accumulation, one is the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into Menaquinone-4 in tissues, and another is cleavage and prenylation within the cerebrum.
Kim Lewis - One of the best experts on this subject based on the ideXlab platform.
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Quinones are growth factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:BackgroundThe human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors.ResultsBy testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a Menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified Menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete Menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically.ConclusionsOur data show that Menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.
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quinones are growth factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a Menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified Menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete Menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that Menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.
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Additional file 5: Table S3. of Quinones are growth factors for the human gut microbiota
2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Sarah Rubin, Jon Clardy, Eric Stewart, Kim LewisAbstract:Quinone-induced bacteria have a disrupted Menaquinone biosynthesis pathway, while related organisms not induced by quinones have a complete pathway. The genomes of the nearest type strains of all E. coli- or quinone-induced cultured bacteria were surveyed manually for the presence of a functional Menaquinone biosynthesis pathway using a published dataset [24]. All organisms induced by E. coli or quinones in earlier co-culture experiments were missing large components of the Menaquinone biosynthesis pathway, while Bacteroides species not induced by E. coli or quinones were predicted to have complete Menaquinone biosynthetic capabilities. No strains were found to have predicted copies of genes in the futalosine pathway, an alternative means to generate Menaquinone. ubiE/menG: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase; menF = Menaquinone-specific isochorismate synthase; menD = 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase; menH = 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase; menY = 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate dehydrogenase; menC = o-succinylbenzoate synthase; menE = o-succinylbenzoic acid--CoA ligase; menB = Naphthoate synthase. menI = 1,4-dihydroxy-2-naphthoyl-CoA hydrolase; menJ = 1,4-dihydroxy-2-naphthoyl-CoA hydrolasein (putative); menA = 1,4-dihydroxy-2-naphthoate polyprenyltransferase; mqnA = Chorismate dehydratase; mqnE = Aminodeoxyfutalosine synthase; mqnC = Cyclic dehypoxanthine futalosine synthase; mqnD = 1,4-dihydroxy-6-naphthoate synthase; mqnZ = 1,4-dihydroxy-6-naphthoate synthase (alternative); mqnX = Aminodeoxyfutalosine deaminase; mqnB = Futalosine hydrolase (EC 3.2.2.26); mtnN = Aminodeoxyfutalosine nucleosidase; mqnL = 1,4-dihydroxy-6-naphthoate carboxy-lyase, UbiD-like; mqnM = 2-heptaprenyl-1,4-naphthoquinone methyltransferase; mqnP = 1,4-naphthoquinone polyprenyltransferase. Data was taken and modified from Racheev, 2016. (XLSX 10 kb
M J Drittijreijnders - One of the best experts on this subject based on the ideXlab platform.
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vitamin k status in human tissues tissue specific accumulation of phylloquinone and Menaquinone 4
British Journal of Nutrition, 1996Co-Authors: H.h.w. Thijssen, M J DrittijreijndersAbstract:We measured the vitamin K status in postmortem human tissues (brain, heart, kidney, liver, lung, pancreas) to see if there is a tissue-specific distribution pattern. Phylloquinone (K1) was recovered in all tissues with relatively high levels in liver, heart and pancreas (medians, 10.6 (4.8), 9.3 (4.2), 28.4 (12.8) pmol(ng)/g wet weight tissue); low levels (< 2 pmol/g) were found in brain, kidney and lung. Menaquinone-4 (MK-4) was recovered from most of the tissues; its levels exceeded the K1 levels in brain and kidney (median, 2.8 ng/g) and equalled K1 in pancreas. Liver, heart and lung were low in MK-4. The higher Menaquinones, MK-6-11, were recovered in the liver samples (n 6), traces of MK-6-9 were found in some of the heart and pancreas samples. The results show that in man there are tissue-specific, vitamin-K distribution patterns comparable to those in the rat. Furthermore, the accumulation of vitamin K in heart, brain and pancreas suggests a hitherto unrecognized physiological function of this vitamin.
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vitamin k distribution in rat tissues dietary phylloquinone is a source of tissue Menaquinone 4
British Journal of Nutrition, 1994Co-Authors: H.h.w. Thijssen, M J DrittijreijndersAbstract:The present study was undertaken to determine whether there is selective tissue distribution of vitamin K in the rat and whether this distribution mirrors the distribution of tissue vitamin K metabolism. The effects of feeding a vitamin K-free diet followed by resupplementation with phylloquinone (K1) were studied. K1 was recovered in all tissues. In K1 -supplemented rats, most tissues accumulated K1 relative to plasma K1 with the highest levels in liver, heart, bone, and cartilaginous tissue (sternum). Low K1 levels were found in the brain. In the K1-free rats, relatively high K1 levels were still found in heart, pancreas, bone and sternum. Surprisingly, Menaquinone-4 (MK-4) was detected in all tissues, with low levels in plasma and liver, and much higher levels in pancreas, salivary gland and sternum. MK-4 levels exceeded K1 levels in brain, pancreas, salivary gland and sternum. Supplementation with K1, orally and by intravenous infusion, caused MK-4 levels to rise. Some accumulation of K1 and MK-4 in the mitochondrial fraction was found for kidney, pancreas and salivary gland. In the liver the higher Menaquinones (MK-6–9) accumulated in the mitochondria. The results indicate that: (1) there is selective tissue distribution of K1 and MK-4, (2) dietary K1 is a source of MK-4. The results also suggest there may be an as yet unrecognized physiological function for vitamin K (MK-4).