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Tomoko Hasegawa, Hanako Ohashi Ikeda, Sachiko Iwai, Yuki Muraoka, Tatsuaki Tsuruyama, Keiko Okamoto-Furuta, Haruyasu Kohda, Akira Kakizuka, Nagahisa Yoshimura
Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular ATP levels, which was canceled by a glycolysis inhibitor...
February 2018: Heliyon
Priya Reddy, Joseph Leong, Ishwarlal Jialal
AIMS: Metabolic Syndrome (MetS) is a cluster of cardio-metabolic risk factors characterized by low-grade inflammation which confers an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Prior studies have linked elevated branched chain amino acids (BCAA) and aromatic amino acids (AAA) with T2DM and CVD. Due to the paucity of data in MetS, the aim of this study was to investigate the status of amino acids as early biomarkers of nascent MetS patients without T2DM and CVD or smoking...
March 9, 2018: Journal of Diabetes and its Complications
Sergio Polakof, Didier Rémond, Jérémie David, Dominique Dardevet, Isabelle Savary-Auzeloux
OBJECTIVES: High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of this study was to elucidate whether elevated BCAA levels are the cause or the consequence of IR and to determine the mechanisms and tissues involved in such a phenotype. METHODS: We performed a 2-mo follow-up on minipigs overfed an HFHS diet and focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues...
November 27, 2017: Nutrition
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Hailong Zhang, Longzhen Cui, Wen Liu, Zhenfeng Wang, Yang Ye, Xue Li, Huijuan Wang
Introduction: Gastric cancer (GC) is a malignant tumor worldwide. As primary pathway for metastasis, the lymphatic system is an important prognostic factor for GC patients. Although the metabolic changes of gastric cancer have been investigated in extensive studies, little effort focused on the metabolic profiling of lymph node metastasis (LNM)-positive or negative GC patients. Objectives: We performed1 H NMR spectrum of GC tissue samples with and without LNM to identify novel potential metabolic biomarkers in the process of LNM of GC...
2018: Metabolomics: Official Journal of the Metabolomic Society
Moran Brenner, Lior Lobel, Ilya Borovok, Nadejda Sigal, Anat A Herskovits
Listeria monocytogenes (Lm) is a saprophyte and intracellular pathogen. Transition to the pathogenic state relies on sensing of host-derived metabolites, yet it remains unclear how these are recognized and how they mediate virulence gene regulation. We previously found that low availability of isoleucine signals Lm to activate the virulent state. This response is dependent on CodY, a global regulator and isoleucine sensor. Isoleucine-bound CodY represses metabolic pathways including branched-chain amino acids (BCAA) biosynthesis, however under BCAA depletion, as occurs during infection, BCAA biosynthesis is upregulated and isoleucine-unbound CodY activates virulence genes...
March 12, 2018: PLoS Genetics
Riccardo Natoli, Nilisha Fernando, Tess Dahlenburg, Haihan Jiao, Riemke Aggio-Bruce, Nigel L Barnett, Juan Manuel Chao de la Barca, Guillaume Tcherkez, Pascal Reynier, Johnny Fang, Joshua A Chu-Tan, Krisztina Valter, Jan Provis, Matt Rutar
Purpose: Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between obesity and retinal inflammation has yet to be assessed. We used the leptin-deficient (ob/ob) mouse to further our understanding of the contribution of obesity to retinal oxidative stress and inflammation...
2018: Molecular Vision
Jeong Sang Yi, Minsuk Kim, Eun-Jung Kim, Byung-Gee Kim
Branched chain amino acids (BCAA) are catabolized into various acyl-CoA compounds, which are key precursors used in polyketide productions. Because of that, BCAA catabolism needs fine tuning of flux balances for enhancing the production of polyketide antibiotics. To enhance BCAA catabolism for pikromycin production in Streptomyces venezuelae ATCC 15439, three key enzymes of BCAA catabolism, 3-ketoacyl acyl carrier protein synthase III, acyl-CoA dehydrogenase, and branched chain α-keto acid dehydrogenase (BCDH) were manipulated...
March 10, 2018: Journal of Industrial Microbiology & Biotechnology
E Yu Bezsudnova, K M Boyko, V O Popov
Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. BCATs are the key enzymes of BCAA metabolism in all organisms. The catalysis proceeds through the ping-pong mechanism with the assistance of the cofactor pyridoxal 5'-phosphate (PLP). BCATs differ from other (S)-selective transaminases (TAs) in 3D-structure and organization of the PLP-binding domain. Unlike other (S)-selective TAs, BCATs belong to the PLP fold type IV and are characterized by the proton transfer on the re-face of PLP, in contrast to the si-specificity of proton transfer in fold type I (S)-selective TAs...
December 2017: Biochemistry. Biokhimii︠a︡
Yuichi Uchino, Masafumi Watanabe, Munenori Takata, Eisuke Amiya, Kensuke Tsushima, Takeshi Adachi, Yukio Hiroi, Toshikazu Funazaki, Issei Komuro
BACKGROUND: We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS: We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT® ) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy...
March 6, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Minjun Xu, Yasuyuki Kitaura, Daichi Shindo, Yoshiharu Shimomura
Branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BDK) suppresses the branched-chain amino acid (BCAA) catabolism by inactivation of the BCKDH complex. The muscle-specific BDK-deficient (BDK-mKO) mice showed accelerated BCAA oxidation in muscle and decreased endurance capacity after training (Xu et al. PLoS One. 12 (2017) e0180989). We here report that BCAA supplementation overcompensated endurance capacity in BDK-mKO mice after training.
March 1, 2018: Bioscience, Biotechnology, and Biochemistry
Shunichi Shiozawa, Takebumi Usui, Kotaro Kuhara, Akira Tsuchiya, Tatsuomi Miyauchi, Teppei Kono, Yukio Shimojima, Shinichi Asaka, Kentaro Yamaguchi, Hajime Yokomizo, Takeshi Shimakawa, Kazuhiko Yoshimatsu, Takao Katsube, Yoshihiko Naritaka
BackgroundandAim: The recommendedind ication of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)is Barcelona Clinic Liver Cancer(BCLC)stage B HCC. But there are some cases in which we do not perform TACE because of liver damage with malnutrition in stage B. So we examined whether branched-chain amino acid (BCAA)improve nutritional status and perform TACE to contribute the prolongation of HCC survival. METHODS: This study included8 8 patients treatedfor liver cirrhosis with HCC...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Natthaporn Takpho, Daisuke Watanabe, Hiroshi Takagi
Valine, which is one of the branched-chain amino acids (BCAAs) essential for humans, is widely used in animal feed, dietary supplements and pharmaceuticals. At the commercial level, valine is usually produced by bacterial fermentation from glucose. However, valine biosynthesis can also proceed in the yeast Saccharomyces cerevisiae, which is a useful microorganism in fermentation industry. In S. cerevisiae, valine biosynthesis is regulated by valine itself via the feedback inhibition of acetohydroxyacid synthase (AHAS), which consists of two subunits, the catalytic subunit Ilv2 and the regulatory subunit Ilv6...
March 3, 2018: Metabolic Engineering
Richelle V Curtis, Julie J M Kim, John Doelman, John P Cant
The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of milk protein yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments...
February 21, 2018: Journal of Dairy Science
Vasim Ahmed, Manoj K Verma, Shashank Gupta, Vibha Mandhan, Nar S Chauhan
Osmotolerance is one of the critical factors for successful survival and colonization of microbes in saline environments. Nonetheless, information about these osmotolerance mechanisms is still inadequate. Exploration of the saline soil microbiome for its community structure and novel genetic elements is likely to provide information on the mechanisms involved in osmoadaptation. The present study explores the saline soil microbiome for its native structure and novel genetic elements involved in osmoadaptation...
2018: Frontiers in Microbiology
M Zacchigna, F Cateni, G Procida, D Zampieri, M G Mamolo
Methoxy polyethylene glycol conjugated with coenzyme Q10 (mPEG)-CoQ10 and analog adducts with amino acids as spacers were synthesized as a new drug delivery systems for CoQ10. Alanine and branched chain amino acids (valine, leucine and isoleucine) were conjugated to mPEG by an amide linkage and to CoQ10 by an ester bond. Recently, branched chain amino acids (BCAAs), which are released along with CoQ10, have received increasing attention as 'anti-fatigue' elements. FT-IR and 1H NMR spectroscopic analysis were useful to characterize the synthesized conjugates...
December 1, 2017: Die Pharmazie
Yaping Shao, Guozhu Ye, Shancheng Ren, Hai-Long Piao, Xinjie Zhao, Xin Lu, Fubo Wang, Ma Wang, Jia Li, Peiyuan Yin, Tian Xia, Chuanliang Xu, Jane J Yu, Yinghao Sun, Guowang Xu
Genetic alterations drive metabolic reprogramming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa...
February 14, 2018: International Journal of Cancer. Journal International du Cancer
Justyna Wolak-Dinsmore, Eke G Gruppen, Irina Shalaurova, Steven P Matyus, Russell P Grant, Ray Gegen, Stephan J L Bakker, James D Otvos, Margery A Connelly, Robin P F Dullaart
OBJECTIVES: Plasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. DESIGN AND METHODS: The performance of the NMR-based BCAA assay was evaluated...
February 9, 2018: Clinical Biochemistry
Qian Yang, Wei Deng, Shipeng Wang, Hongjie Liu, Xuefeng Li, Mingqi Zheng
BACKGROUND: Descurainia sophia L., a problematic weed in winter wheat fields in China, has developed high resistance to tribenuron-methyl. Amino acid substitutions at sites Pro197, Asp376 and Trp574 in the target acetohydroxyacid synthase (AHAS) were primarily responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia plants individually homozygous for a specific resistance mutation (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu or Trp574Leu) in AHAS were purified and generated, and the effects of resistance mutations on D...
February 9, 2018: Pest Management Science
Aurore Martin Agnoux, Angélina El Ghaziri, Thomas Moyon, Anthony Pagniez, Agnès David, Gilles Simard, Patricia Parnet, El Mostafa Qannari, Dominique Darmaun, Jean-Philippe Antignac, Marie-Cécile Alexandre-Gouabau
Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. However, the exact mechanisms underlying offspring metabolic adaptations are not yet fully understood. Specifically, it remains unclear whether the gestation or the lactation is the more vulnerable period to modify offspring metabolic flexibility. We investigated in a rodent model of intrauterine growth restriction (IUGR) induced by maternal protein restriction (R) during gestation which time window of maternal undernutrition (gestation, lactation or gestation-lactation) has more impact on the male offspring metabolomics phenotype...
December 10, 2017: Journal of Nutritional Biochemistry
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