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Makoto Suematsu - One of the best experts on this subject based on the ideXlab platform.
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cystathionine γ lyase deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury
Journal of Biological Chemistry, 2010Co-Authors: Isao Ishii, Noriyuki Akahoshi, Hidenori Yamada, Shintaro Nakano, Takashi Izumi, Makoto SuematsuAbstract:Cysteine is considered a Nonessential Amino Acid in mammals as it is synthesized from methionine via trans-sulfuration. However, premature infants or patients with hepatic failure may require dietary cysteine due to a lack of cystathionine gamma-lyase (CTH), a key trans-sulfuration enzyme. Here, we generated CTH-deficient (Cth(-/-)) mice as an animal model of cystathioninemia/cystathioninuria. Cth(-/-) mice developed normally in general but displayed hypercystathioninemia/hyperhomocysteinemia though not hypermethioninemia. When fed a low cyst(e)ine diet, Cth(-/-) mice showed acute skeletal muscle atrophy (myopathy) accompanied by enhanced gene expression of asparagine synthetase and reduced contents of glutathione in livers and skeletal muscles, and intracellular accumulation of LC3 and p62 in skeletal myofibers; they finally died of severe paralysis of the extremities. Cth(-/-) hepatocytes required cystine in a culture medium and showed greater sensitivity to oxidative stress. Cth(-/-) mice exhibited systemic vulnerability to oxidative injury, which became more prominent when they were fed the low cyst(e)ine diet. These results reveal novel roles of trans-sulfuration previously unrecognized in mice lacking another trans-sulfuration enzyme cystathionine beta-synthase (Cbs(-/-)). Because Cbs(-/-) mice display hyperhomocysteinemia and hypermethioninemia, our results raise questions against the homocysteine-based etiology of CBS deficiency and the current newborn screening for homocysteinemia using Guthrie's method, which detects hypermethioninemia.
Puspitasari Findya - One of the best experts on this subject based on the ideXlab platform.
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Pengaruh Lama Pemasakan terhadap Kadar Protein, Lemak, Profil Asam Amino, dan Asam Lemak Tepung Ikan Sepat Rawa (Trichogaster trichopterus): Effect of Different Cooking Time on Protein and Fat Content, Amino Acid and Fatty Acid Profile of Three Spot Gourami (Trichogaster trichopterus) Fish Flour
'Indonesian Society Fisheries Product Processing', 2020Co-Authors: Adawyah Rabiatul, Khusnul Khotiffah Siti, Puspitasari FindyaAbstract:Three spot gourami (Trichogaster trichopterus) population in South Kalimantan is abundant but not yet utilized optimally. Processing three spot gourami into fish flour is expected to maximize its utilization. This study aimed to understand the effect of different cooking time in three spot gourami fish flour processing on protein and fat content, Amino Acid, and fatty Acid profile. The design of this study was experimental with a completely randomized design method. The protein content was analyzed by kjeldahl method, Amino Acid analyzed by High Performance Liquid Chromatography (HPLC) method, lipid content analyzed by the soxhlet method and fatty Acid analyzed by Gas Chromatography (GC). The treatments used were cooking using a pan for 30 minutes (A), autoclave 20 minutes (B), and autoclave 30 minutes (C). The results showed the treatment affected protein and fat content, as well as Amino Acid and fatty Acid profiles. The highest protein content in treatment C 63.76%, the lowest fat content in treatment B 3.53%. For the Amino Acid profile, lysine is the highest type of essential Amino Acid, while the highest type of Nonessential Amino Acid is glutamic Acid, and in the fatty Acid profile there are 23 types of fatty Acids, the highest is palmitic Acid with an average 21.66%, followed by oleic Acid d 17.49% and linoleic Acid 6.69%.Populasi ikan sepat rawa (Trichogaster trichopterus) di Provinsi Kalimantan Selatan melimpah namun masih belum dimanfaatkan secara maksimal. Pengolahan ikan sepat rawa menjadi tepung ikan diharapkan dapat memaksimalkan pemanfaatannya. Penelitian ini bertujuan untuk menganalisis pengaruh perbedaan lama pemasakan pada proses pengolahan tepung ikan terhadap kadar protein, kadar lemak, profil asam Amino, dan asam lemak tepung ikan sepat rawa. Penelitian menggunakan metode Rancangan Acak Lengkap (RAL) dengan perlakuan pemasakan. Perlakuan yang diberikan adalah pemasakan menggunakan panci selama 30 menit (A), autoklaf 20 menit (B) dan autoklaf 30 menit (C). Hasil penelitian menunjukkan perlakuan memberikan pengaruh terhadap kadar protein dan lemak, serta profil asam Amino dan asam lemak. Kadar protein paling tinggi pada perlakuan C sebesar 63,76%, kadar lemak terendah pada perlakuan B sebesar 3,53%. Untuk profil asam Amino, lisin merupakan jenis asam Amino esensial paling tinggi dari profil asam Amino penyusun protein tepung ikan, sedangkan jenis asam Amino non esensial tertinggi adalah asam glutamat, dan pada profil asam lemak terdapat 23 jenis asam lemak, tertinggi adalah asam palmitat sebesar 21,66%, asam oleat d sebesar 17,49% dan asam linoleat sebesar 6,69%
Craig B Thompson - One of the best experts on this subject based on the ideXlab platform.
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cancer cell metabolism the essential role of the Nonessential Amino Acid glutamine
The EMBO Journal, 2017Co-Authors: Ji Zhang, Natalya N Pavlova, Craig B ThompsonAbstract:Abstract Biochemistry textbooks and cell culture experiments seem to be telling us two different things about the significance of external glutamine supply for mammalian cell growth and proliferation. Despite the fact that glutamine is a Nonessential Amino Acid that can be synthesized by cells from glucose‐derived carbons and Amino Acid‐derived ammonia, most mammalian cells in tissue culture cannot proliferate or even survive in an environment that does not contain millimolar levels of glutamine. Not only are the levels of glutamine in standard tissue culture media at least ten‐fold higher than other Amino Acids, but glutamine is also the most abundant Amino Acid in the human bloodstream, where it is assiduously maintained at approximately 0.5 mM through a combination of dietary uptake, de novo synthesis, and muscle protein catabolism. The complex metabolic logic of the proliferating cancer cells9 appetite for glutamine—which goes far beyond satisfying their protein synthesis requirements—has only recently come into focus. In this review, we examine the diversity of biosynthetic and regulatory uses of glutamine and their role in proliferation, stress resistance, and cellular identity, as well as discuss the mechanisms that cells utilize in order to adapt to glutamine limitation.
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glutamine addiction a new therapeutic target in cancer
Trends in Biochemical Sciences, 2010Co-Authors: David R Wise, Craig B ThompsonAbstract:Most cancers depend on a high rate of aerobic glycolysis for their continued growth and survival. Paradoxically, some cancer cell lines also display addiction to glutamine despite the fact that glutamine is a Nonessential Amino Acid that can be synthesized from glucose. The high rate of glutamine uptake exhibited by glutamine-dependent cells does not appear to result solely from its role as a nitrogen donor in nucleotide and Amino Acid biosynthesis. Instead, glutamine plays a required role in the uptake of essential Amino Acids and in maintaining activation of TOR (target of rapamycin) kinase. Moreover, in many cancer cells, glutamine is the primary mitochondrial substrate and is required for maintenance of mitochondrial membrane potential and integrity and for support of the NADPH production needed for redox control and macromolecular synthesis.
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beyond aerobic glycolysis transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Ralph J Deberardinis, Anthony Mancuso, Evgueni Daikhin, Ilana Nissim, Marc Yudkoff, Suzanne Wehrli, Craig B ThompsonAbstract:Tumor cell proliferation requires rapid synthesis of macromolecules including lipids, proteins, and nucleotides. Many tumor cells exhibit rapid glucose consumption, with most of the glucose-derived carbon being secreted as lactate despite abundant oxygen availability (the Warburg effect). Here, we used 13C NMR spectroscopy to examine the metabolism of glioblastoma cells exhibiting aerobic glycolysis. In these cells, the tricarboxylic Acid (TCA) cycle was active but was characterized by an efflux of substrates for use in biosynthetic pathways, particularly fatty Acid synthesis. The success of this synthetic activity depends on activation of pathways to generate reductive power (NADPH) and to restore oxaloacetate for continued TCA cycle function (anaplerosis). Surprisingly, both these needs were met by a high rate of glutamine metabolism. First, conversion of glutamine to lactate (glutAminolysis) was rapid enough to produce sufficient NADPH to support fatty Acid synthesis. Second, despite substantial mitochondrial pyruvate metabolism, pyruvate carboxylation was suppressed, and anaplerotic oxaloacetate was derived from glutamine. Glutamine catabolism was accompanied by secretion of alanine and ammonia, such that most of the Amino groups from glutamine were lost from the cell rather than incorporated into other molecules. These data demonstrate that transformed cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of Nonessential Amino Acid pools. Rather, glutamine metabolism provides a carbon source that facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.
Suhn-young Im - One of the best experts on this subject based on the ideXlab platform.
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glutamine suppresses dnfb induced contact dermatitis by deactivating p38 mitogen activated protein kinase via induction of mapk phosphatase 1
Journal of Investigative Dermatology, 2013Co-Authors: Otgonzaya Ayush, Suhn-young ImAbstract:L-glutamine (Gln) is a Nonessential Amino Acid that is the most abundant Amino Acid in plasma. Gln has been reported to have an anti-inflammatory activity that involves deactivation of mitogen-activated protein kinases (MAPKs) in a MAPK phosphatase (MKP)-1-dependent manner. This study investigated the role of Gln in the inhibition of DNFB-induced allergic contact dermatitis (CD) in the ears of mice, and specifically the involvement of Gln in p38 MAPK inhibition. Topical application of Gln or the p38 inhibitor, SB202190, suppressed DNFB-induced CD. Gln application inhibited DNFB-induced p38 phosphorylation. Western blot analysis revealed that Gln application resulted in early phosphorylation and protein induction of MKP-1. MKP-1 small interfering RNA (siRNA), but not control siRNA, abrogated Gln-mediated early phosphorylation, protein induction of MKP-1, deactivation of p38, and Gln-mediated suppression of CD. The extracellular signal–regulated kinase (ERK) inhibitor, U0126, blocked Gln-induced MKP-1 phosphorylation and protein induction, as well as Gln suppression of CD. These results suggest that Gln suppresses DNFB-induced CD via deactivation of p38 MAPK through the early induction of MKP-1, the negative regulator of p38, in an ERK-dependent manner.
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glutamine suppresses airway neutrophilia by blocking cytosolic phospholipase a 2 via an induction of mapk phosphatase 1
Journal of Immunology, 2012Co-Authors: Otgonzaya Ayush, Suhn-young Im, Daekyu OhAbstract:Neutrophils are inflammatory cells that may contribute in a crucial way to the pathophysiology of steroid-resistant severe asthma. We previously reported that the Nonessential Amino Acid l-glutamine (Gln) suppressed the recruitment of neutrophils into the airway in a murine model of asthma. In this study, we investigated the mechanisms by which Gln exerts beneficial effects in airway neutrophilia. We used the model we previously developed, which is suitable for examining sequential early asthmatic events, including neutrophil infiltration. Gln suppressed airway neutrophilia in a CXC chemokine-independent way. Airway neutrophilia was associated with cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO) activities. p38 MAPK, the upstream pathway of cPLA2 and 5-LO, played a key role in inducing airway neutrophilia. Gln inhibited not only the phosphorylation of cPLA2 and p38 MAPK but also leukotriene B4 levels in the airways. Gln induced the early induction of MAPK phosphatase-1 (MKP-1) protein, a negative regulator of p38. MKP-1 small interfering RNA abrogated all the effects of Gln. Our results suggest that pathways involving p38/cPLA2/5-LO have a major role in airway neutrophilia. Gln suppresses airway neutrophilia via inhibiting p38 MAPK and its downstream pathways in an MKP-1–dependent way, which may provide a novel therapeutic strategy for pulmonary neutrophilic inflammatory diseases.
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glutamine protects mice from lethal endotoxic shock via a rapid induction of mapk phosphatase 1
Journal of Immunology, 2009Co-Authors: Hyunmi Ko, Sinhye Oh, Hwasuk Bang, Namin Kang, Suhn-young ImAbstract:The Nonessential Amino Acid l-glutamine (Gln) is the most abundant Amino Acid in plasma. Clinical trials have demonstrated that Gln therapy is safe and improves clinical outcomes in critically ill patients. We have previously shown that Gln protect animals from endotoxic shock through the inhibition of cytosolic phospholipase A 2 activity. In this study, we investigated how Gln regulates MAPK activation, as the molecular mechanism underlying Gln-induced cytosolic phospholipase A 2 inactivation. Gln rapidly (within 10 min) inactivated p38 and JNK, but not ERK, by dephosphorylating them only when these MAPKs were phosphorylated in response to LPS in vivo as well as in vitro. Western blot analysis revealed that Gln administration resulted in rapid (∼5 min) phosphorylation and protein induction of MAP kinase phosphatase-1 (MKP-1). MKP-1 siRNA abrogated the Gln-mediated 1) inactivation of p38 and JNK, 2) induction of MKP-1, and 3) protection against endotoxic shock. The ERK inhibitor U0126 blocked Gln-induced MKP-1 phosphorylation and protein induction, as well as Gln’s protective activity against endotoxic shock. These data suggest that Gln exerts a beneficial effect on endotoxic shock by inactivating p38 and JNK via a rapid induction of MKP-1 protein in an ERK-dependent way.
H Lapierre - One of the best experts on this subject based on the ideXlab platform.
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changes in production and mammary metabolism of dairy cows in response to essential and Nonessential Amino Acid infusions
Journal of Dairy Science, 2010Co-Authors: L Doepel, H LapierreAbstract:Abstract This study was undertaken to increase our understanding of the need of the mammary gland for the different types of AA and how the mammary gland alters its metabolism in response to a variable AA supply. Eight lactating Holstein cows (61±4 DIM) were used in a replicated 4 × 4 Latin square balanced for residual effects with 14-d periods. The diet was formulated to supply 100% of the net energy requirement and 72% of the metabolizable protein requirement. The 4 treatments were 1) abomasal infusions of water, 2) essential AA at 359g/d, 3) Nonessential AA at 356g/d, and 4) essential AA at 359g/d+Nonessential AA at 356g/d (total of 715g/d). The infusates had the same AA profile as casein with the exception that Met was increased to maintain a 3:1 ratio of digestible Lys to Met and because of solubility limitations all the Tyr was replaced by Phe and part of the Glu was replaced by Gln. Milk yield and milk protein yield were increased by the essential AA treatments compared with the other treatments. Mammary uptake of β-hydroxybutyrate plus lactate tended to increase with the essential AA treatments, whereas glucose mammary uptake tended to be higher with the Nonessential AA treatments. With the essential AA treatments, the mammary uptake:milk protein output ratio for the group 1 AA (His, Met, Phe, Trp, and Tyr) did not differ from 1 but tended to increase; the ratio for the group 2 AA (Ile, Leu, Lys, and Val) did increase, significantly exceeding unity when essential AA were infused. These results indicate that the mammary gland alters differently its uptake of both AA and energy-yielding nutrients in response to the amount and profile of AA presented to it and that even under situations of protein deficiency Nonessential AA supplementation does not enhance milk and milk protein synthesis.
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changes in production and mammary metabolism of dairy cows in response to essential and Nonessential Amino Acid infusions
Journal of Dairy Science, 2010Co-Authors: L Doepel, H LapierreAbstract:This study was undertaken to increase our understanding of the need of the mammary gland for the different types of AA and how the mammary gland alters its metabolism in response to a variable AA supply. Eight lactating Holstein cows (61+/-4 DIM) were used in a replicated 4 x 4 Latin square balanced for residual effects with 14-d periods. The diet was formulated to supply 100% of the net energy requirement and 72% of the metabolizable protein requirement. The 4 treatments were 1) abomasal infusions of water, 2) essential AA at 359 g/d, 3) Nonessential AA at 356 g/d, and 4) essential AA at 359 g/d+Nonessential AA at 356 g/d (total of 715 g/d). The infusates had the same AA profile as casein with the exception that Met was increased to maintain a 3:1 ratio of digestible Lys to Met and because of solubility limitations all the Tyr was replaced by Phe and part of the Glu was replaced by Gln. Milk yield and milk protein yield were increased by the essential AA treatments compared with the other treatments. Mammary uptake of beta-hydroxybutyrate plus lactate tended to increase with the essential AA treatments, whereas glucose mammary uptake tended to be higher with the Nonessential AA treatments. With the essential AA treatments, the mammary uptake:milk protein output ratio for the group 1 AA (His, Met, Phe, Trp, and Tyr) did not differ from 1 but tended to increase; the ratio for the group 2 AA (Ile, Leu, Lys, and Val) did increase, significantly exceeding unity when essential AA were infused. These results indicate that the mammary gland alters differently its uptake of both AA and energy-yielding nutrients in response to the amount and profile of AA presented to it and that even under situations of protein deficiency Nonessential AA supplementation does not enhance milk and milk protein synthesis.