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https://www.readbyqxmd.com/read/29234669/aminoglycoside-resistance-profile-and-structural-architecture-of-the-aminoglycoside-acetyltransferase-aac-6-im
#1
Clyde A Smith, Monolekha Bhattacharya, Marta Toth, Nichole K Stewart, Sergei B Vakulenko
Aminoglycoside 6'-acetyltransferase-Im (AAC(6')-Im) is the closest monofunctional homolog of the AAC(6')-Ie acetyltransferase of the bifunctional enzyme AAC(6')-Ie/APH(2")-Ia. The AAC(6')-Im acetyltransferase confers 4- to 64-fold higher MICs to 4,6-disubstituted aminoglycosides and the 4,5-disubstituted aminoglycoside neomycin than AAC(6')-Ie, yet unlike AAC(6')-Ie, the AAC(6')-Im enzyme does not confer resistance to the atypical aminoglycoside fortimicin. The structure of the kanamycin A complex of AAC(6')-Im shows that the substrate binds in a shallow positively-charged pocket, with the N6' amino group positioned appropriately for an efficient nucleophilic attack on an acetyl-CoA cofactor...
November 9, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29232514/discovery-of-novel-selective-acetyl-coa-carboxylase-acc-1-inhibitors
#2
Ryo Mizojiri, Moriteru Asano, Daisuke Tomita, Hiroshi Banno, Noriyuki Nii, Masako Sasaki, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Takeo Moriya, Yoshinori Satomi, Hironobu Maezaki
We initiated our structure-activity relationship (SAR) studies for selective ACC1 inhibitors from 1a as a lead compound. SAR studies of bicyclic scaffolds revealed many potent and selective ACC1 inhibitors represented by 1f, however most of them had physicochemical issues, particularly low aqueous solubility and potent CYP inhibition. To address these two issues and improve the drug-likeness of this chemical series, we converted the bicyclic scaffold into a monocyclic framework. Ultimately, this lead us to discover a novel monocyclic derivative 1q as a selective ACC1 inhibitor, which showed highly potent and selective ACC1 inhibition as well as acceptable solubility and CYP inhibition profiles...
December 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232396/fatty-acids-rather-than-hormones-restore-in-vitro-angiogenesis-in-human-male-and-female-endothelial-cells-cultured-in-charcoal-stripped-serum
#3
Claudia Vanetti, Francesco Bifari, Lucia M Vicentini, Maria Grazia Cattaneo
Charcoal-stripped serum (CSS) is a well-accepted method to model effects of sex hormones in cell cultures. We have recently shown that human endothelial cells (ECs) fail to growth and to undergo in vitro angiogenesis when cultured in CSS. However, the mechanism(s) underlying the CSS-induced impairment of in vitro EC properties are still unknown. In addition, whether there is any sexual dimorphism in the CSS-induced EC phenotype remains to be determined. Here, by independently studying human male and female ECs, we found that CSS inhibited both male and female EC growth and in vitro angiogenesis, with a more pronounced effect on male EC sprouting...
2017: PloS One
https://www.readbyqxmd.com/read/29231156/efficient-bio-production-of-citramalate-using-an-engineered-escherichia-coli-strain
#4
Joseph P Webb, S Alison Arnold, Scott Baxter, Stephen J Hall, Graham Eastham, Gill Stephens
Citramalic acid is a central intermediate in a combined biocatalytic and chemocatalytic route to produce bio-based methylmethacrylate, the monomer used to manufacture Perspex and other high performance materials. We developed an engineered E. coli strain and a fed-batch bioprocess to produce citramalate at concentrations in excess of 80 g l-1 in only 65 h. This exceptional efficiency was achieved by designing the production strain and the fermentation system to operate synergistically. Thus, a single gene encoding a mesophilic variant of citramalate synthase from Methanococcus jannaschii, CimA3...
December 12, 2017: Microbiology
https://www.readbyqxmd.com/read/29230863/characterization-of-a-nilaparvata-lugens-st%C3%A3-l-brummer-gene-and-analysis-of-its-role-in-lipid-metabolism
#5
Jinming Zhou, Jing Yan, Keke You, Xia Chen, Zhineng Yuan, Qiang Zhou, Kai Lu
The brummer (bmm) genes encode the lipid storage droplet-associated triacylglycerols (TAG) lipases, which belong to the Brummer/Nutrin subfamily. These enzymes hydrolyze the ester bonds in TAG in lipid metabolism and act in insect energy homeostasis. Exposure to some agricultural chemicals leads to increased fecundity, which necessarily involves lipid metabolism, in some planthopper species. However, the biological roles of bmm in planthopper lipid storage and mobilization have not been investigated. Here, the open reading frame (ORF) of bmm (Nlbmm) was cloned and sequenced from the brown planthopper (BPH; Nilaparvata lugens)...
December 12, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29228177/poly-3-hydroxybutyrate-hyperproduction-by-a-global-nitrogen-regulator-ntrb-mutant-strain-of-paracoccus-denitrificans-pd1222
#6
Alfonso Olaya-Abril, Víctor M Luque-Almagro, Isabel Manso, Andrew J Gates, Conrado Moreno-Vivián, David J Richardson, María Dolores Roldán
Paracoccus denitrificans PD1222 accumulates short-length polyhydroxyalkanoates, poly(3-hydroxybutyrate), under nitrogen deficient conditions. Polyhydroxybutyrate metabolism requires the 3-ketoacyl-CoA thiolase PhaA, the acetoacetyl-CoA dehydrogenase/reductase PhaB, and the synthase PhaC for polymerization. Additionally, P. denitrificans PD1222 grows aerobically with nitrate as sole nitrogen source. Nitrate assimilation is controlled negatively by ammonium through the two-component NtrBC system. NtrB is a sensor kinase that autophosphorylates a histidine residue under low nitrogen concentrations and, in turn transfers a phosphoryl group to an aspartate residue of the response regulator NtrC protein, which acts as a transcriptional activator of the P...
December 6, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29227176/metabolomics-approach-in-the-study-of-the-well-defined-polyherbal-preparation-zyflamend
#7
Eric D Tague, Allen K Bourdon, Amber MacDonald, Maggie S Lookadoo, Edward D Kim, Wesley M White, Paul D Terry, Shawn R Campagna, Brynn H Voy, Jay Whelan
Zyflamend is a highly controlled blend of 10 herbal extracts that synergistically impact multiple cell signaling pathways with anticancer and anti-inflammatory properties. More recently, its effects were shown to also modify cellular energetics, for example, activation of fatty acid oxidation and inhibition of lipogenesis. However, its general metabolic effects in vivo have yet to be explored. The objective of this study was to characterize the tissue specific metabolomes in response to supplementation of Zyflamend in mice, with a comparison of equivalent metabolomics data generated in plasma from humans supplemented with Zyflamend...
December 11, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29224880/the-effect-of-different-treatments-for-early-lactation-hyperketonemia-on-liver-triglycerides-glycogen-and-expression-of-key-metabolic-enzymes-in-dairy-cattle
#8
S Mann, F A Leal Yepes, J J Wakshlag, E Behling-Kelly, J A A McArt
Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism...
December 7, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29224626/development-of-a-bacterial-propionate-biosensor-for-anaerobic-digestion-monitoring
#9
Joseph B Sweeney, Cormac D Murphy, Kevin McDonnell
Monitoring anaerobic digestion (AD) leachate for changes in acetate and propionate concentrations is essential for effective AD operation. In this paper the development of a novel propionate cell-based biosensor is described. A previously designed E. coli mutant (IMD Wldgy) that could selectively determine acetate concentrations in synthetic leachates, based on oxygen uptake measurements, was used as a starting point in the development of a propionate biosensor. However, the propionate-grown IMD Wldgy cells exhibited extremely low propionate:acetate O2 consumption ratios (1:2...
February 2018: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/29221849/molecular-regulation-of-fatty-acid-oxidation-in-skeletal-muscle-during-aerobic-exercise
#10
REVIEW
Anne-Marie Lundsgaard, Andreas Mæchel Fritzen, Bente Kiens
This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondrial fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid (TCA) cycle...
December 5, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29212446/transcriptomics-analysis-of-the-flowering-regulatory-genes-involved-in-the-herbicide-resistance-of-asia-minor-bluegrass-polypogon-fugax
#11
Fengyan Zhou, Yong Zhang, Wei Tang, Mei Wang, Tongchun Gao
BACKGROUND: Asia minor bluegrass (Polypogon fugax, P. fugax), a weed that is both distributed across China and associated with winter crops, has evolved resistance to acetyl-CoA carboxylase (ACCase) herbicides, but the resistance mechanism remains unclear. The goal of this study was to analyze the transcriptome between resistant and sensitive populations of P. fugax at the flowering stage. RESULTS: Populations resistant and susceptible to clodinafop-propargyl showed distinct transcriptome profiles...
December 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29211711/kat2a-coupled-with-the-%C3%AE-kgdh-complex-acts-as-a-histone-h3-succinyltransferase
#12
Yugang Wang, Yusong R Guo, Ke Liu, Zheng Yin, Rui Liu, Yan Xia, Lin Tan, Peiying Yang, Jong-Ho Lee, Xin-Jian Li, David Hawke, Yanhua Zheng, Xu Qian, Jianxin Lyu, Jie He, Dongming Xing, Yizhi Jane Tao, Zhimin Lu
Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29208696/acetyl-coa-carboxylase-1-regulates-endothelial-cell-migration-by-shifting-the-phospholipid-composition
#13
Daniel K Glatzel, Andreas Koeberle, Helmut Pein, Konstantin Loeser, Anna Stark, Nelli Keksel, Oliver Werz, Rolf Mueller, Iris Bischoff, Robert Fuerst
The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid metabolism. In recent years, ACC has been recognized as a promising drug target for treating different diseases. However, the role of ACC in vascular endothelial cells (ECs) has been neglected so far. To characterize the role of ACC we used both the ACC inhibitor soraphen A as chemical tool and a gene silencing approach. We found that ACC1 was the predominant isoform in primary human umbilical vein endothelial cells (HUVECs) and that soraphen A reduced the levels of malonyl-CoA...
December 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29207101/diosgenin-prevents-high-fat-diet-induced-rat-non-alcoholic-fatty-liver-disease-through-the-ampk-and-lxr-signaling-pathways
#14
Silu Cheng, Shufang Liang, Qun Liu, Zhengting Deng, Yuanhui Zhang, Juan Du, Ya'ni Zhang, Shu Li, Binbin Cheng, Changquan Ling
Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207025/anti-obesity-effects-of-pectinase-and-cellulase-enzyme%C3%A2-treated-ecklonia%C3%A2-cava-extract-in-high%C3%A2-fat-diet%C3%A2-fed-c57bl-6n-mice
#15
In-Hye Kim, Jung-Wook Choi, Min-Kyeong Lee, Chang-Ju Kwon, Taek-Jeong Nam
The present study investigated the anti‑obesity effects of enzyme‑treated Ecklonia cava extract (EEc) in C57BL/6N mice with high‑fat diet (HFD)‑induced obesity. The EEc was separated and purified with the digestive enzymes pectinase (Rapidase X‑Press L) and cellulase (Rohament CL) and its effects on the progression of HFD‑induced obesity were examined over 10 weeks. The mice were divided into 6 groups (n=10/group) as follows: Normal diet group, HFD group, mice fed a HFD with 25 mg/kg/day Garcinia cambogia extract and mice fed a HFD with 5, 25 or 150 mg/kg/day EEc (EHD groups)...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205418/transcriptional-regulation-of-acetyl-coa-and-lipid-synthesis-by-pii-protein-in-synechococcus-pcc-7942
#16
Ekta Verma, Sindhunath Chakraborty, Balkrishna Tiwari, Arun K Mishra
PII protein family is widespread in prokaryotes and plants. In this study, impacts of PII deficiency on the synthesis of acetyl CoA and acetyl CoA carboxylase enzyme (ACCase) was analyzed in the Synechococcus sp. PCC 7942 by evaluating the mRNA levels of pyruvate kinase (PK), pyruvate dehydrogenase (PDH), citrate synthase (CS), biotin synthase (BS), biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), carboxyl transferase (CT) α and β subunits. The PII deficient Synechococcus sp. PCC 7942 showed upregulation of all the above-mentioned genes, except CS...
December 5, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29203794/behavioral-impairment-in-shati-nat8l-knockout-mice-via-dysfunction-of-myelination-development
#17
Kazuyuki Sumi, Kyosuke Uno, Hiroshi Noike, Takenori Tomohiro, Yasumaru Hatanaka, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta
We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29201040/caffeoylquinic-acid-rich-extract-of-aster-glehni-f-schmidt-ameliorates-nonalcoholic-fatty-liver-through-the-regulation-of-ppar%C3%AE-and-adiponectin-in-apoe-ko-mice
#18
Yong-Jik Lee, Yoo-Na Jang, Yoon-Mi Han, Hyun-Min Kim, Jong-Min Jeong, Min Jeoung Son, Chang Bae Jin, Hyoung Ja Kim, Hong Seog Seo
Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni. Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor δ, 5' adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPARγ coactivator 1-alpha in liver tissues increased in the groups treated with A...
2017: PPAR Research
https://www.readbyqxmd.com/read/29199584/anti-inflammation-and-lipogenic-inhibition-of-taiwanofungus-salmonea-mycelium-and-grifola-frondosa-fruiting-body
#19
Rao-Chi Chien, Yi-Chi Yang, Eric Icheng Lai, Jeng-Leun Mau
A long-term inflammatory response can cause the development of nonalcoholic steatohepatitis (NASH), which is mainly caused by abnormal metabolism of lipids in the liver. Taiwanofungus salmonea and Grifola frondosa, which are valuable medicinal mushrooms in Taiwan and exhibit many beneficial bioactivities, are used to evaluate effects on immune regulation in Raw 264.7 cells and on NASH-related responses in Hep G2 cells. According to the results, the production of proinflammatory cytokines was effectively decreased, whereas the production of interleukin-10 was increased...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29199089/applying-asymptotic-methods-to-synthetic-biology-modelling-the-reaction-kinetics-of-the-mevalonate-pathway
#20
Mohit P Dalwadi, Marco Garavaglia, Joseph P Webb, John R King, Nigel P Minton
The mevalonate pathway is normally found in eukaryotes, and allows for the production of isoprenoids, a useful class of organic compounds. This pathway has been successfully introduced to Escherichia coli, enabling a biosynthetic production route for many isoprenoids. In this paper, we develop and solve a mathematical model for the concentration of metabolites in the mevalonate pathway over time, accounting for the loss of acetyl-CoA to other metabolic pathways. Additionally, we successfully test our theoretical predictions experimentally by introducing part of the pathway into Cupriavidus necator...
November 30, 2017: Journal of Theoretical Biology
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