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BCAA metabolism

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
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
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
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
Filip Ottosson, Louise Brunkwall, Ulrika Ericson, Peter M Nilsson, Peter Almgren, Céline Fernandez, Olle Melander, Marju Orho-Melander
Context: Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions and altered plasma metabolome may reflect differences in the gut microbiome. Objective: To identify a plasma metabolite profile associated with BMI in a general population and to investigate if such metabolite profile is associated with distinct composition of the gut microbiota. Design: Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age 39y, 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography-mass spectrometry...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
Takaaki Hirota, Masanori Izumi, Shinya Wada, Amane Makino, Hiroyuki Ishida
The vacuolar lytic degradation of proteins releases free amino acids (AAs) that plants can use instead of sugars for respiratory energy production. Autophagy is a major cellular process leading to the transport of proteins into the vacuole for degradation. Here, we examine the contribution of autophagy to the AA metabolism response to sugar starvation in mature leaves of Arabidopsis thaliana. During sugar starvation arising from the exposure of wild-type (WT) plants to darkness, autophagic transport of chloroplast stroma, which contains most of the proteins in a leaf, into the vacuolar lumen was induced within two days...
January 30, 2018: Plant & Cell Physiology
Lun Zhao, Li Deng, Qing Zhang, Xue Jing, Meng Ma, Bin Yi, Jing Wen, Chaozhi Ma, Jinxing Tu, Tingdong Fu, Jinxiong Shen
Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved in SU tolerance. Here, we report a novel SU tolerance mechanism, autophagy, which we call 'homeostatic tolerance,' is involved in amino acid signaling in Arabidopsis. The activation and reversion of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for the activation of autophagy and GCN2...
January 29, 2018: Autophagy
Nicholas P Gannon, Jamie K Schnuck, Roger A Vaughan
Branched-chain amino acids (BCAAs) appear to influence several synthetic and catabolic cellular signaling cascades leading to altered phenotypes in mammals. BCAAs are most notably known to increase protein synthesis through modulating protein translation, explaining their appeal to resistance and endurance athletes for muscle hypertrophy, expedited recovery, and preservation of lean body mass. In addition to anabolic effects, BCAAs may increase mitochondrial content in skeletal muscle and adipocytes, possibly enhancing oxidative capacity...
January 29, 2018: Molecular Nutrition & Food Research
Laura Tedesco, Giovanni Corsetti, Chiara Ruocco, Maurizio Ragni, Fabio Rossi, Michele O Carruba, Alessandra Valerio, Enzo Nisoli
Chronic alcohol consumption promotes mitochondrial dysfunction, oxidative stress, defective protein metabolism, and fat accumulation in hepatocytes (liver steatosis). Inadequate amino-acid metabolism is worsened by protein malnutrition, frequently present in alcohol-consuming patients, with reduced circulating branched-chain amino acids (BCAAs). Here we asked whether dietary supplementation with a specific amino-acid mixture, enriched in BCAAs (BCAAem) and able to promote mitochondrial function in muscle of middle-aged rodents, would prevent mitochondrial dysfunction and liver steatosis in Wistar rats fed on a Lieber-DeCarli ethanol (EtOH)-containing liquid diet...
January 25, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Bingjuan Han, Bingchao Han, Bin Guo, Yingxia Liu, Zhiyang Cao
BACKGROUND: Maple syrup urine disease (MSUD) is a rare metabolic disorder of autosomal recessive inheritance caused by decreased activity of branched-chain α-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the presenting symptoms, clinical course and gene mutation analysis of a Chinese boy with MSUD. METHODS: Plasma amino acid analysis was performed by tandem mass spectrometry and the levels of organic acids in urine were measured with gas chromatography-mass spectrometry...
January 6, 2018: Pediatrics and Neonatology
Julienne C Kaiser, Alyssa N King, Jason C Grigg, Jessica R Sheldon, David R Edgell, Michael E P Murphy, Shaun R Brinsmade, David E Heinrichs
Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon...
January 22, 2018: PLoS Genetics
You Zhang, Bingjie Yin, Runxian Li, Pingli He
Branched-chain keto acids (BCKAs) are derivatives from the first step in the metabolism of branched-chain amino acids (BCAAs) and can provide important information on animal health and disease. Here, a simple, reliable and effective method was developed for the determination of three BCKAs (α-ketoisocaproate, α-keto-β-methylvalerate and α-ketoisovalerate) in serum and muscle samples using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS). The samples were extracted using methanol and separated on a 1...
January 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiaomei Li, Yali Yang, Qing Gao, Min Gao, Yvqiang Lv, Rui Dong, Yi Liu, Kaihui Zhang, Zhongtao Gai
Maple syrup urine disease (MSUD) is an autosomal recessive disorder affecting branched-chain amino acids (BCAAs) metabolism and caused by a defect in the thiamine-dependent enzyme branched chain α-ketoacid dehydrogenase (BCKD) with subsequent accumulation of BCAAs and corresponding branched-chain keto acids (BCKAs) metabolites. Presently, at least 4 genes of BCKDHA, BCKDHB, DLD and DBT have been reported to cause MSUD. Furthermore, more than 265 mutations have been identified as the cause across different populations worldwide...
January 6, 2018: Metabolic Brain Disease
Liyan Fan, Paishiun N Hsieh, David R Sweet, Mukesh K Jain
Regulation of nutrient intake, utilization, and storage exhibits a circadian rhythmicity that allows organisms to anticipate and adequately respond to changes in the environment across day/night cycles. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are important modulators of metabolism and metabolic health - for example, their catabolism yields carbon substrates for gluconeogenesis during periods of fasting. Krüppel-like factor 15 (KLF15) has recently emerged as a critical transcriptional regulator of BCAA metabolism, and the absence of this transcription factor contributes to severe pathologies such as Duchenne muscular dystrophy and heart failure...
December 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Golaleh Asghari, Hossein Farhadnejad, Farshad Teymoori, Parvin Mirmiran, Maryam Tohidi, Fereidoun Azizi
BACKGROUND: The aim of this study was to investigate the association between branched-chain amino acid (BCAA) intake and markers of insulin metabolism in adults. METHODS: This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 1205 subjects, aged ≥20 years, who were followed-up for a mean of 2.3 years. Dietary intake of BCAAs, including valine, leucine, and isoleucine, was determined using a valid and reliable food frequency questionnaire...
December 27, 2017: Journal of Diabetes
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