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Branched-chain amino acid

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https://www.readbyqxmd.com/read/29779826/the-bckdh-kinase-and-phosphatase-integrate-bcaa-and-lipid-metabolism-via-regulation-of-atp-citrate-lyase
#1
Phillip J White, Robert W McGarrah, Paul A Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L Lapworth, Inna Astapova, Sarah A Hannou, Tabitha George, Michelle Arlotto, Lyra B Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A Herman, R Max Wynn, David T Chuang, Christopher B Newgard
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K...
May 11, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29779472/effect-of-body-weight-on-metabolic-hormones-and-fatty-acid-metabolism-in-follicular-fluid-of-women-undergoing-in-vitro-fertilization-a-pilot-study
#2
Laurice Bou Nemer, Haolin Shi, Bruce Richard Carr, Ruth Ann Word, Orhan Bukulmez
INTRODUCTION: Obesity is an epidemic affecting more than one-third of adults in the United States. Obese women experience decreased fertility, explained in part by oocyte quality. Since follicular fluid (FF) provides an important microenvironment for oocyte growth, we sought to evaluate the effect of increased body weight on FF levels of 11 metabolic hormones and fatty acid metabolism. METHODS: The FF was collected from 25 women (10 normal weight, 10 overweight, and 5 obese) with diminished ovarian reserve undergoing in vitro fertilization (IVF) following a minimal stimulation protocol...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29779155/prioritising-risk-factors-for-type-2-diabetes-causal-inference-through-genetic-approaches
#3
REVIEW
Laura B L Wittemans, Luca A Lotta, Claudia Langenberg
PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown...
May 19, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29774776/memory-deficit-in-an-object-location-task-after-mild-tbi-is-associated-with-impaired-early-object-exploration-and-both-are-restored-by-branched-chain-amino-acid-dietary-therapy
#4
Rosalia Paterno, Hannah Metheny, Akiva S Cohen
The relation between traumatic brain injury (TBI) and memory dysfunction is well established, yet imprecise. Here, we investigate whether mild TBI causes a specific deficit in spatial episodic memory. Fifty-eight (29 TBI, 29 Sham) mice were run in a spatial recognition task. To determine which phase of memory might be affected in our task, we assessed rodent performance at three different delay times (3 min, 1 hour, and 24 hours). We found that sham and TBI mice performed equally well at 3 minutes, but TBI mice had significantly impaired spatial recognition memory after a delay time of one hour...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29767564/interorgan-metabolic-crosstalk-in-human-insulin-resistance
#5
Sofiya Gancheva, Tomas Jelenik, Elisa Álvarez-Hernández, Michael Roden
Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29764289/divergent-induction-of-branched-chain-aminotransferases-and-phosphorylation-of-branched-chain-keto-acid-dehydrogenase-is-a-potential-mechanism-coupling-bcka-mediated-astrocyte-activation-to-bcaa-depletion-mediated-cognitive-deficit-after-tbi
#6
Guoqiang Xing, Ming Ren, Ajay Verma
Deficient branched chain amino acids (BCAAs) are implicated in cognitive dysfunction after traumatic brain injury (TBI). The mechanism remains unknown. BCAAs are catabolized by neuron-specific cytosolic and astrocyte-specific mitochondrial branched chain aminotransferases (BCATc, BCATm) to generate glutamate and branched-chain keto-acids (BCKAs) that are metabolized via the mitochondrial branched-chain-keto-acid dehydrogenase (BCKD) whose activity is regulated by its phosphorylation state. BCKD phosphorylation by BCKD kinase (BCKDK) inactivates BCKD and cause neuro-cognitive dysfunction, whereas de-phosphorylation by specific phosphatase restores BCKD activity...
May 15, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29762873/l-ornithine-l-aspartate-for-prevention-and-treatment-of-hepatic-encephalopathy-in-people-with-cirrhosis
#7
REVIEW
Ee Teng Goh, Caroline S Stokes, Sandeep S Sidhu, Hendrik Vilstrup, Lise Lotte Gluud, Marsha Y Morgan
BACKGROUND: Hepatic encephalopathy is a common complication of cirrhosis and has high associated morbidity and mortality. The condition is classified as overt if it is clinically apparent or minimal if only evident though psychometric testing. The exact pathogenesis of this syndrome is unknown although ammonia is thought to play a key role. L-ornithine L-aspartate has ammonia-lowering properties and may, therefore, benefit people with cirrhosis and hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions in people with cirrhosis and hepatic encephalopathy...
May 15, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29762522/dietary-pattern-and-plasma-bcaa-variations-in-healthy-men-and-women-results-from-the-karmen-study
#8
Benedikt Merz, Lara Frommherz, Manuela J Rist, Sabine E Kulling, Achim Bub, Bernhard Watzl
Branched-chain amino acids (BCAA) in plasma are discussed as risk factors for the onset of several diseases. Information about the contribution of the overall diet to plasma BCAA concentrations is controversial. Our objective was to investigate which dietary pattern is associated with plasma BCAA concentrations and whether other additional nutrients besides BCAA further characterize this dietary pattern. Based on the cross-sectional KarMeN study, fasting plasma amino acid (AA) concentrations, as well as current and habitual dietary intake were assessed in 298 healthy individuals...
May 15, 2018: Nutrients
https://www.readbyqxmd.com/read/29755574/branched-chain-amino-acids-in-health-and-disease-metabolism-alterations-in-blood-plasma-and-as-supplements
#9
REVIEW
Milan Holeček
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29754208/serum-amino-acid-profiling-in-patients-with-alkaptonuria-before-and-after-treatment-with-nitisinone
#10
A S Davison, B P Norman, E A Smith, J Devine, J Usher, A T Hughes, M Khedr, A M Milan, J A Gallagher, L R Ranganath
BACKGROUND: Alkaptonuria (AKU) is a rare inherited disorder of the tyrosine metabolic pathway. Our group is evaluating the use of the homogentisic acid-lowering agent nitisinone in patients with AKU. A major biochemical consequence of this treatment is hypertyrosinaemia. Herein we report the concentration of 20 serum amino acids over a 36-month period pre- and post-treatment with nitisinone. METHODS: Fasting serum samples were collected at baseline (pre-nitisinone), 3 (2 mg nitisinone every other day), 6, 12, 24 and 36 (2 mg nitisinone daily) months...
May 13, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29753318/successful-pregnancy-in-maple-syrup-urine-disease-a-case-report-and-review-of-the-literature
#11
Sarah Catharina Grünert, Stefanie Rosenbaum-Fabian, Anke Schumann, Karl Otfried Schwab, Nadja Mingirulli, Ute Spiekerkoetter
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive disorder of branched-chain amino acid metabolism. Patients with MSUD are at risk of life-threatening metabolic decompensations with ketoacidosis and encephalopathy. These episodes are often triggered by physiological stress. Only few cases of pregnancies in MSUD mothers have been reported so far. CASE PRESENTATION: We present the favorable outcome of a pregnancy in a woman with classical MSUD...
May 12, 2018: Nutrition Journal
https://www.readbyqxmd.com/read/29752915/increase-in-insulin-secretion-and-decrease-in-muscle-degradation-by-fat-free-milk-intake-are-attenuated-by-physical-exercise
#12
Tetsuo Yamada, Masami Matsuzaki, Akira Tanaka
BACKGROUND: Protein intake, particularly branched chain amino acids (BCAAs), and exercise have opposing actions on insulin secretion, but the same action on protein anabolism. We examined the effects of BCAA-rich fat-free milk intake and/or exercise on levels of insulin secretion and indices related to muscle protein metabolism in order to assess the potency of dietary and exercise therapies against metabolic and locomotive disorders. METHODS: Eight adult female volunteers participated in all four 24 h experiments; control diet intake with or without exercise, and fat-free milk-containing diet intake with or without exercise...
May 9, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29746639/branched-chain-amino-acids-are-the-primary-limiting-amino-acids-in-the-diets-of-endurance-trained-men-after-a-bout-of-prolonged-exercise
#13
Hiroyuki Kato, Katsuya Suzuki, Makoto Bannai, Daniel R Moore
Background: The indicator amino acid oxidation (IAAO) method estimates the protein intake required to maximize whole-body protein synthesis and identify the daily protein requirement in a variety of populations. However, it is unclear whether the greater requirements for endurance athletes previously determined by the IAAO reflect an increased demand for all or only some amino acids. Objective: The aim of this study was to determine the primary rate-limiting amino acids in endurance-trained athletes after prolonged exercise, by measuring the oxidation of ingested [1-13C]phenylalanine in response to variable amino acid intake...
May 9, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29743968/altered-redox-homeostasis-in-branched-chain-amino-acid-disorders-organic-acidurias-and-homocystinuria
#14
REVIEW
Eva Richard, Lorena Gallego-Villar, Ana Rivera-Barahona, Alfonso Oyarzábal, Belén Pérez, Pilar Rodríguez-Pombo, Lourdes R Desviat
Inborn errors of metabolism (IEMs) are a group of monogenic disorders characterized by dysregulation of the metabolic networks that underlie development and homeostasis. Emerging evidence points to oxidative stress and mitochondrial dysfunction as major contributors to the multiorgan alterations observed in several IEMs. The accumulation of toxic metabolites in organic acidurias, respiratory chain, and fatty acid oxidation disorders inhibits mitochondrial enzymes and processes resulting in elevated levels of reactive oxygen species (ROS)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743863/metabolic-fingerprinting-of-joint-tissue-of-collagen-induced-arthritis-cia-rat-in-vitro-high-resolution-nmr-nuclear-magnetic-resonance-spectroscopy-based-analysis
#15
Niraj Kumar Srivastava, Shikha Sharma, Rajkumar Sharma, Neeraj Sinha, Sudhir Kumar Mandal, Deepak Sharma
Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29742810/metabolic-reconstructions-identify-plant-3-methylglutaconyl-coa-hydratase-that-is-crucial-for-branched-chain-amino-acid-catabolism-in-mitochondria
#16
Scott Latimer, Yubing Li, Thuong T H Nguyen, Eric Soubeyrand, Abdelhak Fatihi, Christian G Elowsky, Anna Block, Eran Pichersky, Gilles J Basset
The proteinogenic branched-chain amino acids (BCAAs) leucine, isoleucine and valine are essential nutrients for mammals. In plants, BCAAs double as alternative energy sources when carbohydrates become limiting, the catabolism of BCAAs providing electrons to the respiratory chain and intermediates to the tricarboxylic acid cycle. Yet, the actual architecture of the degradation pathways of BCAAs is not well understood. In this study, gene network modeling in Arabidopsis and rice, and plant-prokaryote comparative genomics detected candidates for 3-methylglutaconyl-CoA hydratase (4...
May 9, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29740775/evaluation-of-plasma-biomarkers-of-inflammation-in-patients-with-maple-syrup-urine-disease
#17
Giselli Scaini, Tássia Tonon, Carolina F Moura de Souza, Patricia F Schuck, Gustavo C Ferreira, João Quevedo, João Seda Neto, Tatiana Amorim, Jose S Camelo, Ana Vitoria Barban Margutti, Rafael Hencke Tresbach, Fernanda Sperb-Ludwig, Raquel Boy, Paula F V de Medeiros, Ida Vanessa D Schwartz, Emilio Luiz Streck
Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that affects branched-chain amino acid (BCAA) catabolism and is associated with acute and chronic brain dysfunction. Recent studies have shown that inflammation may be involved in the neuropathology of MSUD. However, these studies have mainly focused on single or small subsets of proteins or molecules. Here we performed a case-control study, including 12 treated-MSUD patients, in order to investigate the plasmatic biomarkers of inflammation, to help to establish a possible relationship between these biomarkers and the disease...
May 8, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29739976/nadh-nadph-bi-cofactor-utilizing-and-thermoactive-ketol-acid-reductoisomerase-from-sulfolobus-acidocaldarius
#18
Chin-Yu Chen, Tzu-Ping Ko, Kuan-Fu Lin, Bo-Lin Lin, Chun-Hsiang Huang, Cheng-Hung Chiang, Jia-Cherng Horng
Ketol-acid reductoisomerase (KARI) is a bifunctional enzyme in the second step of branched-chain amino acids biosynthetic pathway. Most KARIs prefer NADPH as a cofactor. However, KARI with a preference for NADH is desirable in industrial applications including anaerobic fermentation for the production of branched-chain amino acids or biofuels. Here, we characterize a thermoacidophilic archaeal Sac-KARI from Sulfolobus acidocaldarius and present its crystal structure at a 1.75-Å resolution. By comparison with other holo-KARI structures, one sulphate ion is observed in each binding site for the 2'-phosphate of NADPH, implicating its NADPH preference...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29738774/characterization-of-two-2-isopropylmalate-synthase-homologs-from-thermus-thermophilus-hb27
#19
Ayako Yoshida, Saori Kosono, Makoto Nishiyama
2-Isopropylmalate synthase (IPMS) catalyzes the first step of leucine biosynthesis and is regulated via feedback inhibition by leucine. The thermophilic bacterium, Thermus thermophilus HB27, has two IPMS homologous genes: TTC0847 and TTC0849, both of which are in the branched-chain amino acid biosynthetic gene cluster. Since enzymes involved in the leucine biosynthetic pathway are evolutionarily related to those in isoleucine biosynthesis, TTC0847 and TTC0849 are expected to function as IPMS or citramalate synthase, which is the first enzyme in the isoleucine biosynthetic pathway from pyruvate...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29738448/on-the-evolution-of-specificity-in-members-of-the-yeast-amino-acid-transporter-family-as-parts-of-specific-metabolic-pathways
#20
REVIEW
Christos Gournas, Alexandros Athanasopoulos, Vicky Sophianopoulou
In the recent years, molecular modeling and substrate docking, coupled with biochemical and genetic analyses have identified the substrate-binding residues of several amino acid transporters of the yeast amino acid transporter (YAT) family. These consist of (a) residues conserved across YATs that interact with the invariable part of amino acid substrates and (b) variable residues that interact with the side chain of the amino acid substrate and thus define specificity. Secondary structure sequence alignments showed that the positions of these residues are conserved across YATs and could thus be used to predict the specificity of YATs...
May 8, 2018: International Journal of Molecular Sciences
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