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Takeyori Saheki - One of the best experts on this subject based on the ideXlab platform.
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effects of supplementation on food intake body weight and hepatic metabolites in the citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mouse model of human citrin deficiency
Molecular Genetics and Metabolism, 2012Co-Authors: Takeyori Saheki, Kanako Inoue, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Sumie Furuie, Eishi Kuroda, Miharu Ushikai, Akihiro AsakawaAbstract:The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, Sodium glutamate, Sodium Pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of Sodium Pyruvate, alanine, Sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by Sodium Pyruvate, while alanine and Sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and Sodium glutamate, as well as Sodium Pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight.
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metabolomic analysis reveals hepatic metabolite perturbations in citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mice a model of human citrin deficiency
Molecular Genetics and Metabolism, 2011Co-Authors: Takeyori Saheki, Tomiko Kuhara, Morimasa Ohse, Kanako Inoue, Anmi Tushima, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Kazuhiro EtoAbstract:The citrin/mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, making it a suitable model of human citrin deficiency. In the present study, we investigated metabolic disturbances in the livers of wild-type, citrin (Ctrn) knockout, mGPD knockout, and Ctrn/mGPD double-knockout mice following oral sucrose versus saline administration using metabolomic approaches. By using gas chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry, we found three general groupings of metabolite changes in the livers of the double-knockout mice following sucrose administration that were subsequently confirmed using liquid chromatography/mass spectrometry or enzymatic methods: a marked increase of hepatic glycerol 3-phosphate, a generalized decrease of hepatic tricarboxylic acid cycle intermediates, and alterations of hepatic amino acid levels related to the urea cycle or lysine catabolism including marked increases in citrulline and lysine. Furthermore, concurrent oral administration of Sodium Pyruvate with sucrose ameliorated the hyperammonemia induced by sucrose, as had been shown previously, as well as almost completely normalizing the hepatic metabolite perturbations found. Overall, we have identified additional metabolic disturbances in double-KO mice following oral sucrose administration, and provided further evidence for the therapeutic use of Sodium Pyruvate in our mouse model of citrin deficiency.
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therapeutic approaches for patients with adult onset type ii citrullinemia ctln2 effectiveness of treatment with low carbohydrate diet and Sodium Pyruvate
Rinshō shinkeigaku Clinical neurology, 2010Co-Authors: Masahide Yazaki, Keiko Kobayashi, Shuichi Ikeda, Takeyori SahekiAbstract:Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive disease characterized by highly elevated plasma levels of citrulline and ammonia due to the urea cycle dysfunction associated with citrin deficiency. Patients with CTLN2 show various neurological symptoms with hyperammonemia closely resembling those of hepatic encephalopathy. Since 1990, 26 CTLN2 patients (17 males and 9 females) have been admitted and treated at Shinshu University Hospital. Twelve of the 26 patients received living related partial liver transplantation (LRLT). After LRLT, neurological symptoms soon disappeared, and all patients returned to their previous social lives. Among the 14 patients that did not undergo LRLT, 6 died of intractable encephalopathy or the development of hepatic cancer, but 8 patients have had relatively good clinical courses (follow-up range 0.5-8 years) with oral intake of L-arginine and low-carbohydrate and relatively protein-rich diet. Six patients have been also given Sodium Pyruvate and the frequency of attacks of encephalopathy markedly decreased in 5 of 6 patients. Our observations indicated that liver transplantation is a very promising type of therapy but that other therapeutic approaches, including low-carbohydrate diet and Pyruvate, are being established.
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citrin deficiency and current treatment concepts
Molecular Genetics and Metabolism, 2010Co-Authors: Takeyori Saheki, Kozo Mutoh, Kanako Inoue, Anmi Tushima, Keiko KobayashiAbstract:In this paper, we describe the historical aspects of citrin and citrin deficiency, characteristic food preference and food aversion of citrin-deficient subjects, and carbohydrate toxicity in relation to ureogenesis and issues of the conventional treatment procedures for hyperammonemia in citrin deficiency, leading to current treatment concepts for citrin deficiency. We also emphasize the importance of a citrin deficiency mouse model in elucidating the pathophysiology and developing novel therapeutics based on the pathophysiology, such as Sodium Pyruvate.
Kanako Inoue - One of the best experts on this subject based on the ideXlab platform.
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effects of supplementation on food intake body weight and hepatic metabolites in the citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mouse model of human citrin deficiency
Molecular Genetics and Metabolism, 2012Co-Authors: Takeyori Saheki, Kanako Inoue, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Sumie Furuie, Eishi Kuroda, Miharu Ushikai, Akihiro AsakawaAbstract:The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, Sodium glutamate, Sodium Pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of Sodium Pyruvate, alanine, Sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by Sodium Pyruvate, while alanine and Sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and Sodium glutamate, as well as Sodium Pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight.
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metabolomic analysis reveals hepatic metabolite perturbations in citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mice a model of human citrin deficiency
Molecular Genetics and Metabolism, 2011Co-Authors: Takeyori Saheki, Tomiko Kuhara, Morimasa Ohse, Kanako Inoue, Anmi Tushima, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Kazuhiro EtoAbstract:The citrin/mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, making it a suitable model of human citrin deficiency. In the present study, we investigated metabolic disturbances in the livers of wild-type, citrin (Ctrn) knockout, mGPD knockout, and Ctrn/mGPD double-knockout mice following oral sucrose versus saline administration using metabolomic approaches. By using gas chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry, we found three general groupings of metabolite changes in the livers of the double-knockout mice following sucrose administration that were subsequently confirmed using liquid chromatography/mass spectrometry or enzymatic methods: a marked increase of hepatic glycerol 3-phosphate, a generalized decrease of hepatic tricarboxylic acid cycle intermediates, and alterations of hepatic amino acid levels related to the urea cycle or lysine catabolism including marked increases in citrulline and lysine. Furthermore, concurrent oral administration of Sodium Pyruvate with sucrose ameliorated the hyperammonemia induced by sucrose, as had been shown previously, as well as almost completely normalizing the hepatic metabolite perturbations found. Overall, we have identified additional metabolic disturbances in double-KO mice following oral sucrose administration, and provided further evidence for the therapeutic use of Sodium Pyruvate in our mouse model of citrin deficiency.
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citrin deficiency and current treatment concepts
Molecular Genetics and Metabolism, 2010Co-Authors: Takeyori Saheki, Kozo Mutoh, Kanako Inoue, Anmi Tushima, Keiko KobayashiAbstract:In this paper, we describe the historical aspects of citrin and citrin deficiency, characteristic food preference and food aversion of citrin-deficient subjects, and carbohydrate toxicity in relation to ureogenesis and issues of the conventional treatment procedures for hyperammonemia in citrin deficiency, leading to current treatment concepts for citrin deficiency. We also emphasize the importance of a citrin deficiency mouse model in elucidating the pathophysiology and developing novel therapeutics based on the pathophysiology, such as Sodium Pyruvate.
Krzysztof Matyjaszewski - One of the best experts on this subject based on the ideXlab platform.
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fully oxygen tolerant atom transfer radical polymerization triggered by Sodium Pyruvate
Chemical Science, 2020Co-Authors: Grzegorz Szczepaniak, Matylda łagodzinska, Sajjad Dadashisilab, Adam Gorczynski, Krzysztof MatyjaszewskiAbstract:ATRP (atom transfer radical polymerization) is one of the most robust reversible deactivation radical polymerization (RDRP) systems. However, the limited oxygen tolerance of conventional ATRP impedes its practical use in an ambient atmosphere. In this work, we developed a fully oxygen-tolerant PICAR (photoinduced initiators for continuous activator regeneration) ATRP process occurring in both water and organic solvents in an open reaction vessel. Continuous regeneration of the oxidized form of the copper catalyst with Sodium Pyruvate through UV excitation allowed the chemical removal of oxygen from the reaction mixture while maintaining a well-controlled polymerization of N-isopropylacrylamide (NIPAM) or methyl acrylate (MA) monomers. The polymerizations of NIPAM were conducted with 250 ppm (with respect to the monomer) or lower concentrations of CuBr2 and a tris[2-(dimethylamino)ethyl]amine ligand. The polymers were synthesized to nearly quantitative monomer conversions (>99%), high molecular weights (Mn > 270 000), and low dispersities (1.16 < Đ < 1.44) in less than 30 min under biologically relevant conditions. The reported method provided a well-controlled ATRP (Đ = 1.16) of MA in dimethyl sulfoxide despite oxygen diffusion from the atmosphere into the reaction system.
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synthesis of polymer bioconjugates via photoinduced atom transfer radical polymerization under blue light irradiation
ACS Macro Letters, 2018Co-Authors: Zhenhua Wang, Sushil Lathwal, Alan E. Enciso, Antonina Simakova, Subha R. Das, Alan J. Russell, Krzysztof MatyjaszewskiAbstract:A rapid blue-light-induced atom transfer radical polymerization (ATRP) was conducted in a biologically friendly environment. Well-controlled polymerization of oligo(ethylene oxide) methyl ether methacrylate (OEOMA) was successfully performed in aqueous media (1X PBS) under irradiation by blue LED strips. With 10.0 mW/cm2 intensity output at 450 nm, >90% conversion was achieved in 2 h in the presence of a system comprising glucose, glucose oxidase, and Sodium Pyruvate. Poly(OEOMA) was synthesized with predetermined Mn and low dispersities using low ppm of Cu catalysts. Importantly, secondary structures of proteins, as analyzed by circular dichroism (CD), were preserved under blue-light irradiation due to its lower energy output. The aqueous blue-light ATRP technique was applied to biological systems by synthesizing well-defined protein–polymer and DNA–polymer hybrids by the “grafting-from” method.
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a breathing atom transfer radical polymerization fully oxygen tolerant polymerization inspired by aerobic respiration of cells
Angewandte Chemie, 2018Co-Authors: Alan E. Enciso, Alan J. Russell, Krzysztof MatyjaszewskiAbstract:The first well-controlled aqueous atom-transfer radical polymerization (ATRP) conducted in the open air is reported. This air-tolerant ATRP was enabled by the continuous conversion of oxygen to carbon dioxide catalyzed by glucose oxidase (GOx), in the presence of glucose and Sodium Pyruvate as sequential sacrificial substrates. Controlled polymerization using initiators for continuous activator regeneration (ICAR) ATRP of oligo(ethylene oxide) methyl ether methacrylate (OEOMA, Mn =500) yielded polymers with low dispersity (1.09≤Đ≤1.29) and molecular weights (MWs) close to theoretical values in the presence of Pyruvate. Without added Pyruvates, lower MWs were observed due to generation of new chains by H2 O2 formed by reaction of O2 with GOx. Successful chain extension of POEOMA500 macroinitiator with OEOMA300 (Đ≤1.3) and Bovine Serum Albumin bioconjugates (Đ≤1.22) confirmed a well-controlled polymerization. The reactions in the open air in larger scale (25 mL) were also successful.
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Synthesis of Polymer Bioconjugates via Photoinduced Atom Transfer Radical Polymerization under Blue Light Irradiation
2018Co-Authors: Zhenhua Wang, Sushil Lathwal, Alan E. Enciso, Antonina Simakova, Subha R. Das, Alan J. Russell, Krzysztof MatyjaszewskiAbstract:A rapid blue-light-induced atom transfer radical polymerization (ATRP) was conducted in a biologically friendly environment. Well-controlled polymerization of oligo(ethylene oxide) methyl ether methacrylate (OEOMA) was successfully performed in aqueous media (1X PBS) under irradiation by blue LED strips. With 10.0 mW/cm2 intensity output at 450 nm, >90% conversion was achieved in 2 h in the presence of a system comprising glucose, glucose oxidase, and Sodium Pyruvate. Poly(OEOMA) was synthesized with predetermined Mn and low dispersities using low ppm of Cu catalysts. Importantly, secondary structures of proteins, as analyzed by circular dichroism (CD), were preserved under blue-light irradiation due to its lower energy output. The aqueous blue-light ATRP technique was applied to biological systems by synthesizing well-defined protein–polymer and DNA–polymer hybrids by the “grafting-from” method
Hiromi Ono - One of the best experts on this subject based on the ideXlab platform.
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effects of supplementation on food intake body weight and hepatic metabolites in the citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mouse model of human citrin deficiency
Molecular Genetics and Metabolism, 2012Co-Authors: Takeyori Saheki, Kanako Inoue, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Sumie Furuie, Eishi Kuroda, Miharu Ushikai, Akihiro AsakawaAbstract:The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, Sodium glutamate, Sodium Pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of Sodium Pyruvate, alanine, Sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by Sodium Pyruvate, while alanine and Sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and Sodium glutamate, as well as Sodium Pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight.
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metabolomic analysis reveals hepatic metabolite perturbations in citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mice a model of human citrin deficiency
Molecular Genetics and Metabolism, 2011Co-Authors: Takeyori Saheki, Tomiko Kuhara, Morimasa Ohse, Kanako Inoue, Anmi Tushima, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Kazuhiro EtoAbstract:The citrin/mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, making it a suitable model of human citrin deficiency. In the present study, we investigated metabolic disturbances in the livers of wild-type, citrin (Ctrn) knockout, mGPD knockout, and Ctrn/mGPD double-knockout mice following oral sucrose versus saline administration using metabolomic approaches. By using gas chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry, we found three general groupings of metabolite changes in the livers of the double-knockout mice following sucrose administration that were subsequently confirmed using liquid chromatography/mass spectrometry or enzymatic methods: a marked increase of hepatic glycerol 3-phosphate, a generalized decrease of hepatic tricarboxylic acid cycle intermediates, and alterations of hepatic amino acid levels related to the urea cycle or lysine catabolism including marked increases in citrulline and lysine. Furthermore, concurrent oral administration of Sodium Pyruvate with sucrose ameliorated the hyperammonemia induced by sucrose, as had been shown previously, as well as almost completely normalizing the hepatic metabolite perturbations found. Overall, we have identified additional metabolic disturbances in double-KO mice following oral sucrose administration, and provided further evidence for the therapeutic use of Sodium Pyruvate in our mouse model of citrin deficiency.
Natsumi Katsura - One of the best experts on this subject based on the ideXlab platform.
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effects of supplementation on food intake body weight and hepatic metabolites in the citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mouse model of human citrin deficiency
Molecular Genetics and Metabolism, 2012Co-Authors: Takeyori Saheki, Kanako Inoue, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Sumie Furuie, Eishi Kuroda, Miharu Ushikai, Akihiro AsakawaAbstract:The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, Sodium glutamate, Sodium Pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of Sodium Pyruvate, alanine, Sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by Sodium Pyruvate, while alanine and Sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and Sodium glutamate, as well as Sodium Pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight.
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metabolomic analysis reveals hepatic metabolite perturbations in citrin mitochondrial glycerol 3 phosphate dehydrogenase double knockout mice a model of human citrin deficiency
Molecular Genetics and Metabolism, 2011Co-Authors: Takeyori Saheki, Tomiko Kuhara, Morimasa Ohse, Kanako Inoue, Anmi Tushima, Hiromi Ono, Natsumi Katsura, Mana Yokogawa, Yukari Yoshidumi, Kazuhiro EtoAbstract:The citrin/mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, making it a suitable model of human citrin deficiency. In the present study, we investigated metabolic disturbances in the livers of wild-type, citrin (Ctrn) knockout, mGPD knockout, and Ctrn/mGPD double-knockout mice following oral sucrose versus saline administration using metabolomic approaches. By using gas chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry, we found three general groupings of metabolite changes in the livers of the double-knockout mice following sucrose administration that were subsequently confirmed using liquid chromatography/mass spectrometry or enzymatic methods: a marked increase of hepatic glycerol 3-phosphate, a generalized decrease of hepatic tricarboxylic acid cycle intermediates, and alterations of hepatic amino acid levels related to the urea cycle or lysine catabolism including marked increases in citrulline and lysine. Furthermore, concurrent oral administration of Sodium Pyruvate with sucrose ameliorated the hyperammonemia induced by sucrose, as had been shown previously, as well as almost completely normalizing the hepatic metabolite perturbations found. Overall, we have identified additional metabolic disturbances in double-KO mice following oral sucrose administration, and provided further evidence for the therapeutic use of Sodium Pyruvate in our mouse model of citrin deficiency.