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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
Ekaterina Yu Bezsudnova, Daria V Dibrova, Alena Yu Nikolaeva, Tatiana V Rakitina, Vladimir O Popov
New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity...
February 14, 2018: Journal of Biotechnology
Yuan Xu, Weiming Yu, Taotao Yang, Miaozun Zhang, Chao Liang, Xianlei Cai, Qinshu Shao
As one form of branched chain amino-acid transaminase(BCAT) enzymes, It has been found that up-regulation of BCAT1 is associated with poor prognosis in numerous types of tumors, but studies on the role of BCAT1 expression in gastric cancer(GC) are rare. The aim of this study was to detect BCAT1 expression in (GC) and to analyze its association with prognosis of GC patients. Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and mRNA levels of BCAT1 were validated by immunohistochemistry (IHC) and Real-Time quantitative PCR (RT-qPCR) in GC tissues and adjacent noncancerous tissues (ANCT)...
February 12, 2018: Human Pathology
James E Radcliffe, Jay J Dunsford, Jessica Cid, Valerio Fasano, Michael J Ingleson
The relative (to BEt3) hydride ion affinity (HIA) of a series of acridine borenium salts has been calculated, with some HIAs found to be similar to that for [Ph3C]+. The HIA at the acridine C9 position is controlled by both acridine and the boron substituents, the latter presumably affecting the strength of the B=N bond in the acridane-BY2 products from hydride transfer. Through a range of hydride abstraction benchmarking reactions against organic hydride donors the experimental HIA of [F5acr-BCat]+ (cat = catechol, F5acr = 1,2,3,4,7-pentafluoroacridine) has been confirmed to be extremely high and closely comparable to that of [Ph3C]+...
December 26, 2017: Organometallics
T Ebata, S Hirano, M Konishi, K Uesaka, Y Tsuchiya, M Ohtsuka, Y Kaneoka, M Yamamoto, Y Ambo, Y Shimizu, F Ozawa, A Fukutomi, M Ando, Y Nimura, M Nagino
BACKGROUND: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. METHODS: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location...
February 2018: British Journal of Surgery
Ryan A Mace, William E Mansbach
INTRODUCTION: The prevalence of cognitive, sensory, and physical impairments is expected to grow alongside increasing life expectancy. These chronic conditions pose challenges for geriatric assessment. We examined whether Brief Cognitive Assessment Tool (BCAT) modifications to accommodate visual and motor limitations would retain strong validity for identifying mild cognitive impairment (MCI) and dementia. METHOD: Psychometric analyses were performed on archival data (N = 458) from community-dwelling older adults and residents of assisted living facilities and nursing homes in Maryland, USA (age ≥ 50 years)...
January 30, 2018: Journal of Clinical and Experimental Neuropsychology
Eun-Mi Kim, Joon Ho Park, Byung-Gee Kim, Joo-Hyun Seo
Several (R)-selective ω-aminotransferases (R-ωATs) have been reported. The existence of additional R-ωATs having different sequence characteristics from previous ones is highly expected. In addition, it is generally accepted that R-ωATs are variants of aminotransferase group III. Based on these backgrounds, sequences in RefSeq database were scored using family profiles of branched-chain amino acid aminotransferase (BCAT) and d-alanine aminotransferase (DAT) to predict and identify putative R-ωATs. Sequences with two profile analysis scores were plotted on two-dimensional score space...
March 2018: Enzyme and Microbial Technology
Sarah K Hammer, José L Avalos
Isobutanol and other branched-chain higher alcohols (BCHAs) are promising advanced biofuels derived from the degradation of branched-chain amino acids (BCAAs). The yeast Saccharomyces cerevisiae is a particularly attractive host for the production of BCHAs due to its high tolerance to alcohols and prevalent use in the bioethanol industry. Degradation of BCAAs begins with transamination reactions, catalyzed by branched-chain amino acid transaminases (BCATs) located in the mitochondria (Bat1p) and cytosol (Bat2p)...
November 2017: Metabolic Engineering
James González, Geovani López, Stefany Argueta, Ximena Escalera-Fanjul, Mohammed El Hafidi, Carlos Campero-Basaldua, Joseph Strauss, Lina Riego-Ruiz, Alicia González
Saccharomyces cerevisiae harbors BAT1 and BAT2 paralogous genes that encode branched chain aminotransferases and have opposed expression profiles and physiological roles . Accordingly, in primary nitrogen sources such as glutamine, BAT1 expression is induced, supporting Bat1-dependent valine-isoleucine-leucine (VIL) biosynthesis, while BAT2 expression is repressed. Conversely, in the presence of VIL as the sole nitrogen source, BAT1 expression is hindered while that of BAT2 is activated, resulting in Bat2-dependent VIL catabolism...
November 2017: Genetics
Adonia E Papathanassiu, Jeong-Hun Ko, Martha Imprialou, Marta Bagnati, Prashant K Srivastava, Hong A Vu, Danilo Cucchi, Stephen P McAdoo, Elitsa A Ananieva, Claudio Mauro, Jacques Behmoaras
Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors; however, the function of BCATs in macrophages is unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity. Selective inhibition of BCAT1 activity results in decreased oxygen consumption and glycolysis. This decrease is associated with reduced IRG1 levels and itaconate synthesis, suggesting involvement of BCAA catabolism through the IRG1/itaconate axis within the tricarboxylic acid cycle in activated macrophages...
July 12, 2017: Nature Communications
Chikako Fujii, Kazutoshi Miyashita, Masanori Mitsuishi, Masaaki Sato, Kentaro Fujii, Hiroyuki Inoue, Aika Hagiwara, Sho Endo, Asuka Uto, Masaki Ryuzaki, Motowo Nakajima, Tohru Tanaka, Masanori Tamaki, Ayako Muraki, Toshihide Kawai, Hiroshi Itoh
Recently, sarcopenia has attracted attention as therapeutic target because it constitutes a risk factor for metabolic and cardiovascular diseases. We focused 5-aminolevulinic acid (ALA) which act as electron carriers in the mitochondrial electron transport system. The mice that received ALA for 8 weeks gained muscle strength and endurance, and exhibited increased muscle mass and mitochondrial amount. Administration of ALA to sarcopenia mice aged 100 weeks and chronic kidney disease (CKD) model mice also increased muscle mass and improved physical performance...
June 21, 2017: Scientific Reports
Weimin Xuan, Peter G Schultz
The use of noncanonical amino acids (ncAAs) to control the viability of an organism provides a strategy for the development of conditional "kill switches" for live vaccines or engineered human cells. We report an approach inspired by the posttranslational acetylation/deacetylation of lysine residues, in which a protein encoded by a gene with an in-frame nonsense codon at an essential lysine can be expressed in its native state only upon genetic incorporation of N-ϵ-acetyl-l-Lys (AcK), and subsequent enzymatic deacetylation in the host cell...
July 24, 2017: Angewandte Chemie
Justin E Sperringer, Adele Addington, Susan M Hutson
This review aims to provide a historical reference of branched-chain amino acid (BCAA) metabolism and provide a link between peripheral and central nervous system (CNS) metabolism of BCAAs. Leucine, isoleucine, and valine (Leu, Ile, and Val) are unlike most other essential amino acids (AA), being transaminated initially in extrahepatic tissues, and requiring interorgan or intertissue shuttling for complete catabolism. Within the periphery, BCAAs are essential AAs and are required for protein synthesis, and are key nitrogen donors in the form of Glu, Gln, and Ala...
June 2017: Neurochemical Research
Antonius F Eichhorn, Sonja Fuchs, Marco Flock, Todd B Marder, Udo Radius
The reactivity of N-heterocyclic carbenes (NHCs) and cyclic alkyl amino carbenes (cAACs) with arylboronate esters is reported. The reaction with NHCs leads to the reversible formation of thermally stable Lewis acid/base adducts Ar-B(OR)2 ⋅NHC (Add1-Add6). Addition of cAAC(Me) to the catecholboronate esters 4-R-C6 H4 -Bcat (R=Me, OMe) also afforded the adducts 4-R-C6 H4 Bcat⋅cAAC(Me) (Add7, R=Me and Add8, R=OMe), which react further at room temperature to give the cAAC(Me) ring-expanded products RER1 and RER2...
April 7, 2017: Angewandte Chemie
M W Thairu, I H Skidmore, R Bansal, E Nováková, T E Hansen, H Li-Byarlay, S A Wickline, A K Hansen
RNA interference (RNAi) has emerged as a promising method for validating gene function; however, its utility in nonmodel insects has proven problematic, with delivery methods being one of the main obstacles. This study investigates a novel method of RNAi delivery in aphids, the aerosolization of short interfering RNA (siRNA)-nanoparticle complexes. By using nanoparticles as a siRNA carrier, the likelihood of cellular uptake is increased, when compared to methods previously used in insects. To determine the efficacy of this RNAi delivery system, siRNAs were aerosolized with and without nanoparticles in three aphid species: Acyrthosiphon pisum, Aphis glycines and Schizaphis graminum...
June 2017: Insect Molecular Biology
Yacong Bo, Xueyuan Zhang, Youli Wang, Jie You, Han Cui, Yiwei Zhu, Wei Pang, Wei Liu, Yugang Jiang, Quanjun Lu
OBJECTIVE: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. METHODS: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules...
January 10, 2017: Nutrients
William E Mansbach, Ryan A Mace, Kristen M Clark
Background/Study Context: Whereas computer-assisted cognitive rehabilitation (CR) programs show promise as tools for improving cognition in certain populations, there is not a consensus regarding their efficacy. This study focuses on restorative CR, a treatment designed to improve cognitive functioning affected by progressive brain changes due to disease or aging, through computer-assisted cognitive exercises. The purpose of this study was to investigate the efficacy of a computer-assisted restorative CR intervention for improving cognitive functioning in older rehabilitation patients with relatively mild cognitive deficits...
January 2017: Experimental Aging Research
Farshad Sharifi, Hossein Fakhrzadeh, Mehdi Varmaghani, Seyed Masoud Arzaghi, Mahtab Alizadeh Khoei, Farshad Farzadfar, Parisa Taheri Tanjani
BACKGROUND: The prevalence of cognitive impairment and dementia is increasing in Iran and the world. There is no study available on the prevalence of dementia at the national level in Iran. This study aimed to report the rate of dementia at the national level in Iran. METHODS: The National Elderly Health Survey (NEHS) was a cross-sectional study with multistage cluster random sampling on people aged ≥ 60 years in Iran. Dementia was diagnosed by trained general practitioners using Brief Cognitive Assessment Tool (BCAT)...
December 2016: Archives of Iranian Medicine
M E Conway, S M Hutson
The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur...
2016: Advances in Neurobiology
Yoshiyuki Tanaka, Fumihiro Nakashima, Erasmus Kirii, Tanjuro Goto, Yuichi Yoshida, Ken-Ichiro Yasuba
This research reveals that the up-regulated expression of multiple capsaicinoid biosynthetic genes in pericarp tissue leads to the elevation of total capsaicinoid content in chili pepper fruit. Capsaicinoids are health-functional compounds that are produced uniquely in chili pepper fruits. A high capsaicinoid level is one of the major parameters determining the commercial quality and health-promoting properties of chili peppers. To investigate the mechanisms responsible for its high contents, we compared an extremely pungent cultivar 'Trinidad Moruga Scorpion Yellow' (MY) with other cultivars of different pungency levels (Fushimi-amanaga, Takanotsume, Red Habanero)...
February 2017: Plant Cell Reports
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