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Branched chain amino acid

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https://www.readbyqxmd.com/read/29146470/combination-of-type-ii-fatty-acid-biosynthesis-enzymes-and-thiolases-supports-a-functional-%C3%AE-oxidation-reversal
#1
James M Clomburg, Stephanie C Contreras, Alexander Chou, Justin B Siegel, Ramon Gonzalez
An engineered reversal of the β-oxidation cycle (r-BOX) and the fatty acid biosynthesis (FAB) pathway are promising biological platforms for advanced fuel and chemical production in part due to their iterative nature supporting the synthesis of various chain length products. While diverging in their carbon-carbon elongation reaction mechanism, iterative operation of each pathway relies on common chemical conversions (reduction, dehydration, and reduction) differing only in the attached moiety (acyl carrier protein (ACP) in FAB vs Coenzyme A in r-BOX)...
November 13, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#2
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29143783/metformin-potentiates-the-benefits-of-dietary-restraint-a-metabolomic-study
#3
Marta Riera-Borrull, Anabel García-Heredia, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Noemí Cabré, Elisabet Cuyàs, Fedra Luciano-Mateo, Jordi Camps, Javier A Menendez, Jorge Joven
Prevention of the metabolic consequences of a chronic energy-dense/high-fat diet (HFD) represents a public health priority. Metformin is a strong candidate to be incorporated in alternative therapeutic approaches. We used a targeted metabolomic approach to assess changes related to the multi-faceted metabolic disturbances provoked by HFD. We evaluated the protective effects of metformin and explored how pro-inflammatory and metabolic changes respond when mice rendered obese, glucose-intolerant and hyperlipidemic were switched to diet reversal with or without metformin...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142820/excessive-by-product-formation-a-key-contributor-to-low-isobutanol-yields-of-engineered-saccharomyces-cerevisiae-strains
#4
N Milne, S A Wahl, A J A van Maris, J T Pronk, J M Daran
It is theoretically possible to engineer Saccharomyces cerevisiae strains in which isobutanol is the predominant catabolic product and high-yielding isobutanol-producing strains are already reported by industry. Conversely, isobutanol yields of engineered S. cerevisiae strains reported in the scientific literature typically remain far below 10% of the theoretical maximum. This study explores possible reasons for these suboptimal yields by a mass-balancing approach. A cytosolically located, cofactor-balanced isobutanol pathway, consisting of a mosaic of bacterial enzymes whose in vivo functionality was confirmed by complementation of null mutations in branched-chain amino acid metabolism, was expressed in S...
December 2016: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29142170/characterization-of-a-rat-model-of-moderate-liver-dysfunction-based-on-alpha-naphthylisothiocyanate-induced-cholestasis
#5
Melanie K Bothe, Christoph Meyer, Udo Mueller, Jean-Christophe Queudot, Virginie Roger, Johannes Harleman, Martin Westphal
Plasma amino acid level changes occur in mild, moderate and severe stages of liver injury in human patients. In animal models, however, data are mainly restricted to severe liver injury models in rats. Here we present the characterization of a rat model of moderate liver dysfunction secondary to alpha-napthylisothiocyanate (ANIT)-induced cholestasis. Rats treated with 30 mg/kg/day ANIT for 3 weeks exhibited a time-dependent increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin levels and a decrease in albumin concentration...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#6
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29135487/update-on-endocrine-aspects-of-childhood-obesity
#7
Charumathi Baskaran, Nurgun Kandemir
PURPOSE OF REVIEW: Although childhood obesity has leveled off in the last decade, 'severe obesity' continues to be on the rise. Various genetic, environmental and hormonal factors contribute to obesity. This article reviews the most current understanding of obesity's multifactorial origin and recent recommendations for its management in childhood and adolescence. RECENT FINDINGS: Epigenetics plays a key role in transmitting obesity risk to offspring. Single-nucleotide polymorphisms at genetic loci for adipokines and their receptors are associated with obesity...
November 11, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29132733/enhanced-nutrient-supply-to-very-low-birth-weight-infants-is-associated-with-higher-blood-amino-acid-concentrations-and-improved-growth
#8
Kenneth Strømmen, Alexander Haag, Sissel J Moltu, Marit B Veierød, Elin W Blakstad, Britt Nakstad, Astrid N Almaas, Kristin Brække, Arild E Rønnestad, Hannelore Daniel, Christian A Drevon, Per O Iversen
BACKGROUND & AIMS: Customized nutrient supply is vital to ensure optimal growth among very low birth weight infants (birth weight < 1500 g). The supply of amino acids is especially important due to their impact on protein synthesis and growth. The objectives of this study were to evaluate the impact of enhanced nutrition on growth, blood concentrations of amino acids, and explore possible associations between amino acid concentrations and common neonatal morbidities. We hypothesized higher amino acids levels and growth velocity among infants on enhanced nutrient supply...
April 2017: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/29123168/clinical-parameters-and-gut-microbiome-changes-before-and-after-surgery-in-thoracic-aortic-dissection-in-patients-with-gastrointestinal-complications
#9
Shuai Zheng, Shulin Shao, Zhiyu Qiao, Xue Chen, Chunmei Piao, Ying Yu, Feng Gao, Jie Zhang, Jie Du
Thoracic aortic dissection (TAAD) is one of the most common types of aortic diseases. Although surgery remains the main method of treatment, the high rate of postoperative gastrointestinal complications significantly influences the effects of surgery and the recovery process. Moreover, the mechanisms underlying this disease remain unclear. To address these problems, we examined changes in the gut microbiota in 40 thoracic aortic dissection patients with abdominal complications after surgery. Levels of white blood cells (WBC), neutrophile granulocytes (NE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were higher in all patients after surgery...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122443/identification-of-serum-metabolites-associated-with-obesity-and-traditional-risk-factors-for-metabolic-disease-in-chinese-adults
#10
S M Wang, R Y Yang, M Wang, F S Ji, H X Li, Y M Tang, W X Chen, J Dong
BACKGROUND AND AIMS: Obesity is a major worldwide health problem and is often associated with many metabolic diseases. Levels of several serum-specific metabolites may be altered in patients with these metabolic diseases. We aimed to investigate the associations of serum metabolite levels with obesity and traditional risk factors for metabolic disease in Chinese individuals. METHODS AND RESULTS: Six-hundred Chinese individuals undergoing annual physical exams were recruited and categorized into overweight/obese and control groups (1:1 ratio)...
October 3, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29118722/branched-chain-amino-acid-negatively-regulates-klf15-expression-via-pi3k-akt-pathway
#11
Yunxia Liu, Weibing Dong, Jing Shao, Yibin Wang, Meiyi Zhou, Haipeng Sun
Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29118705/oxaliplatin-induced-hyperammonemic-encephalopathy-in-a-patient-with-metastatic-pancreatic-cancer-a-case-report
#12
Takatsugu Ogata, Hironaga Satake, Misato Ogata, Yukimasa Hatachi, Hisateru Yasui
Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) on day 1, repeated every 2 weeks...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29108956/the-mouse-gm853-gene-encodes-a-novel-enzyme-leucine-decarboxylase
#13
Ana Lambertos, Bruno Ramos-Molina, David Cerezo, Andrés J López-Contreras, Rafael Peñafiel
Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently incorporated into the ODC/AZINs family is the murine Gm853, which is located in the same chromosome as AZIN2, and whose biochemical function is still unknown. By means of transfection assays of HEK293T cells with a plasmid containing the coding region of Gm853, we show here that unlike ODC, GM853 was a stable protein that was not able to decarboxylate l-ornithine or l-lysine and that did not act as an antizyme inhibitor...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29108416/chlorflavonin-targets-acetohydroxyacid-synthase-catalytic-subunit-ilvb1-for-synergistic-killing-of-mycobacterium-tuberculosis
#14
Nidja Rehberg, Herve Sergi Akone, Thomas R Ioerger, German Erlenkamp, Georgios Daletos, Holger Gohlke, Peter Proksch, Rainer Kalscheuer
The flavonoid natural compound chlorflavonin was isolated from the endophytic fungus Mucor irregularis, which was obtained from the Cameroonian medicinal plant Moringa stenopetala. Chlorflavonin exhibited strong growth inhibitory activity in vitro against Mycobacterium tuberculosis (MIC90 1.56 μM) while exhibiting no cytotoxicity towards the human cell lines MRC-5 and THP-1 up to concentrations of 100 µM. Mapping of resistance-mediating mutations employing whole-genome sequencing, chemical supplementation assays, molecular docking studies as well as enzymatic characterization revealed that chlorflavonin specifically inhibits the acetohydroxyacid synthase catalytic subunit IlvB1, causing combined auxotrophies to branched chain amino acids and to pantothenic acid...
November 6, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29108327/evaluation-of-the-branched-chain-amino-acid-to-tyrosine-ratio-prior-to-treatment-as-a-prognostic-predictor-in-patients-with-liver-cirrhosis
#15
Toru Ishikawa, Michitaka Imai, Masayoshi Ko, Hiroki Sato, Yujiro Nozawa, Tomoe Sano, Akito Iwanaga, Keiichi Seki, Terasu Honma, Toshiaki Yoshida
This study evaluated whether the branched-chain amino acid-to-tyrosine ratio (BTR) is a prognostic predictive factor in patients with liver cirrhosis by determining the relationship of the BTR with event-free survival in a retrospective, observational cohort study. The medical records of patients with liver cirrhosis who visited our institution from February 2000 to May 2012 were examined. Events due to liver cirrhosis were defined as death, worsening of esophageal and/or gastric varices, hepatocellular carcinoma, and liver failure...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104034/distribution-of-the-branched-chain-%C3%AE-ketoacid-dehydrogenase-complex-e1%C3%AE-subunit-and-glutamate-dehydrogenase-in-the-human-brain-and-their-role-in-neuro-metabolism
#16
Jonathon Hull, Marcela Usmari Moraes, Emma Brookes, Seth Love, Myra E Conway
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised...
November 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29100177/acinetobacter-baumannii-k13-and-k73-capsular-polysaccharides-differ-only-in-k-unit-side-branches-of-novel-non-2-ulosonic-acids-di-n-acetylated-forms-of-either-acinetaminic-acid-or-8-epiacinetaminic-acid
#17
Johanna J Kenyon, Anastasiya A Kasimova, Anna Notaro, Nikolay P Arbatsky, Immacolata Speciale, Alexander S Shashkov, Cristina De Castro, Ruth M Hall, Yuriy A Knirel
Structures of capsular polysaccharides of Acinetobacter baumannii isolates carrying KL13 and KL73 gene clusters were established. The closely related KL73 and KL13 gene clusters differ only by one gene in the module responsible for synthesis of the non-2-ulosonic acids. The K13 and K73 polysaccharides differ only in a single side-chain sugar, which is either 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-altro- or -d-glycero-l-altro-non-2-ulosonic acid [di-N-acetylated forms of acinetaminic acid (Aci5Ac7Ac) or 8-epiacinetaminic acid (8eAci5Ac7Ac), respectively]...
November 27, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29090929/age-and-sex-effects-on-plasma-metabolite-association-networks-in-healthy-subjects
#18
Alessia Vignoli, Leonardo Tenori, Claudio Luchinat, Edoardo Saccenti
In the era of precision medicine, the analysis of simple information like sex and age can increase the potential to better diagnose and treat conditions that occur more frequently in one of the two sexes, present sex-specific symptoms and outcomes, or are characteristic of a specific age group. We present here study of the association networks constructed from an array of 22 plasma metabolites measured on a cohort of 844 healthy blood donors. Through differential network analysis we show that specific association networks can be associated with sex and age: different connectivity patterns where observed suggesting sex-related variability in several metabolic pathways (branched-chain amino acids, ketone bodies and propanoate metabolism)...
November 1, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29075976/specific-plasma-amino-acid-disturbances-associated-with-metabolic-syndrome
#19
Marta Siomkajło, Jacek Rybka, Magdalena Mierzchała-Pasierb, Andrzej Gamian, Joanna Stankiewicz-Olczyk, Marek Bolanowski, Jacek Daroszewski
PURPOSE: The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. METHODS: Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(-): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed...
October 26, 2017: Endocrine
https://www.readbyqxmd.com/read/29075574/perinatal-western-type-diet-and-associated-gestational-weight-gain-alter-postpartum-maternal-mood
#20
Jessica L Bolton, Melanie G Wiley, Bailey Ryan, Samantha Truong, Melva Strait, Dana Creighton Baker, Nancy Y Yang, Olga Ilkayeva, Thomas M O'Connell, Shelley W Wroth, Cristina L Sánchez, Geeta Swamy, Christopher Newgard, Cynthia Kuhn, Staci D Bilbo, Leigh Ann Simmons
INTRODUCTION: The role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western-type diet (high in fat and branched-chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A). METHODS: Mouse dams were fed one of four diets (high-fat/high BCAA, low-fat/high BCAA, high-fat, and low-fat) prior to mating and throughout gestation and lactation...
October 2017: Brain and Behavior
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