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ATP synthesis

Ali A Kermani, Rana Roy, Chai Gopalasingam, Klaudia I Kocurek, Trushar R Patel, Luke J Alderwick, Gurdyal S Besra, Klaus Fütterer
A growing body of evidence implicates the mycobacterial capsule - the outermost layer of the mycobacterial cell envelope - in modulation of the host immune response and virulence of mycobacteria. Mycobacteria synthesize the dominant capsule component, α(1→4)-linked glucan, via three interconnected, and potentially redundant metabolic pathways. Here, we report the crystal structure of the Mycobacterium smegmatis TreS-Pep2 complex, containing trehalose synthase (TreS) and maltokinase (Pep2), which convert trehalose to maltose-1-phosphate as part of the TreS-Pep2-GlgE pathway...
March 15, 2019: Journal of Biological Chemistry
Gleb A Bazilevsky, Hayley C Affronti, Xuepeng Wei, Sydney L Campbell, Kathryn E Wellen, Ronen Marmorstein
ATP-citrate lyase (ACLY) is the predominant source of nucleocytosolic acetyl-CoA, a fundamental building block of carbon metabolism in eukaryotes. ACLY is aberrantly regulated in many cancers, cardiovascular disease, and metabolic disorders. However, the molecular mechanisms determining ACLY activity and function are unclear. To this end, we investigated the role of the uncharacterized ACLY C-terminal citrate synthase homology domain (CSHD) in the mechanism of acetyl-CoA formation. Using recombinant and purified ACLY and a suite of biochemical and biophysical approaches, including analytical ultracentrifugation, dynamic light scattering, and thermal stability assays, we demonstrate that the C-terminus maintains ACLY tetramerization, a conserved and essential quaternary structure in vitro and likely also in vivo...
March 15, 2019: Journal of Biological Chemistry
Gaomin Feng, Beibei Liu, Jinghang Li, Tianlei Cheng, Zhanglong Huang, Xianhua Wang, Heping Peace Cheng
Respiring mitochondria undergo an intermittent electrical and chemical excitation called mitochondrial flash (mitoflash), which transiently uncouples mitochondrial respiration from ATP production. How a mitoflash is generated and what specific role it plays in bioenergetics remain incompletely understood. Here, we investigate mitoflash biogenesis in isolated cardiac mitochondria by varying the respiratory states and substrate supply and by dissecting the involvement of different electron transfer chain (ETC) complexes...
March 15, 2019: Journal of General Physiology
Jamal Bouitbir, Gerda M Sanvee, Miljenko V Panajatovic, François Singh, Stephan Krähenbühl
Statins lower the serum low-density lipoprotein cholesterol and prevent cardiovascular events by inhibiting 3-hydroxy-3-methyl-glutaryl-CoA reductase. Although the safety of statins is documented, many patients ingesting statins may suffer from skeletal muscle-associated symptoms (SAMS). Importantly, SAMS are a common reason for stopping the treatment with statins. Statin-associated muscular symptoms include fatigue, weakness and pain, possibly accompanied by elevated serum creatine kinase activity. The most severe muscular adverse reaction is the potentially fatal rhabdomyolysis...
March 12, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Atsuyoshi Yamakita, YuanTao Liu, Masamitsu Futai, Atsuko Iwamoto-Kihara
The γ subunit located at the center of ATP synthase (FO F1 ) plays critical roles in catalysis. Escherichia coli mutant with Pro substitution of the γ subunit residue γLeu218, which are located the rotor shaft near the c subunit ring, decreased NADH-driven ATP synthesis activity and ATP hydrolysis-dependent H+ transport of membranes to ~60% and ~40% of the wild type, respectively, without affecting FO F1 assembly. Consistently, the mutant was defective in growth by oxidative phosphorylation, indicating that energy coupling is impaired by the mutation...
March 12, 2019: Biochimica et Biophysica Acta. Bioenergetics
Jean Pierre Oses, Alexandre Pastoris Müller, Nathan Ryzewski Strogulski, Julia D Moreira, Ana Elisa Böhmer, Gisele Hansel, Randhall Bruce Carteri, João Vicente Busnello, Afonso Kopczynski, Marcelo Salimen Rodolphi, Diogo Onofre Souza, Luis Valmor Portela
Generalized seizures trigger excessive neuronal firing that imposes large demands on the brain glucose/lactate availability and utilization, which synchronization requires an integral mitochondrial oxidative capability. We investigated whether a single convulsive crisis affects brain glucose/lactate availability and mitochondrial energy production. Adult male Wistar rats received a single injection of pentylentetrazol (PTZ, 60 mg/kg, i.p.) or saline. The cerebrospinal fluid (CSF) levels of glucose and lactate, mitochondrial respirometry, [14 C]-2-deoxy-D-glucose uptake, glycogen content and cell viability in hippocampus were measured...
March 11, 2019: Epilepsy Research
Quentin M Dudley, Connor J Nash, Michael C Jewett
Isoprenoids are an attractive class of metabolites for enzymatic synthesis from renewable substrates. However, metabolic engineering of microorganisms for monoterpenoid production is limited by the need for time-consuming, and often non-intuitive, combinatorial tuning of biosynthetic pathway variations to meet design criteria. Towards alleviating this limitation, the goal of this work was to build a modular, cell-free platform for construction and testing of monoterpenoid pathways, using the fragrance and flavoring molecule limonene as a model...
2019: Synthetic Biology
Wen-Fa Zhang, Ze-Hao Gong, Meng-Bo Wu, Helen Chan, Yu-Jin Yuan, Ning Tang, Qiang Zhang, Ming-Jun Miao, Wei Chang, Zhi Li, Zheng-Guo Li, Liang Jin, Wei Deng
Tomato fruit are especially susceptible to chilling injury (CI) when continuously exposed to temperatures below 12 °C. In this study, integrative comparative analyses of transcriptomics and metabolomics data were performed to uncover the regulatory network in CI tomato fruit. Metabolite profiling analysis found that 7 amino acids, 27 organic acids, 16 of sugars and 22 other compounds had a significantly different content while transcriptomics data showed 1735 differentially expressed genes (DEGs) were down-regulated and 1369 were up-regulated in cold-stored fruit...
March 14, 2019: Scientific Reports
Alexandra J Harvey
Mitochondria, originally of bacterial origin, are highly dynamic organelles that have evolved a symbiotic relationship within eukaryotic cells. Mitochondria undergo dynamic, stage-specific restructuring and redistribution during oocyte maturation and preimplantation embryo development, necessary to support key developmental events. Mitochondria also fulfil a wide range of functions beyond ATP synthesis, including the production of intracellular reactive oxygen species and calcium regulation, and are active participants in the regulation of signal transduction pathways...
May 1, 2019: Reproduction: the Official Journal of the Society for the Study of Fertility
Amy H Sullivan, David M Dranow, Peter S Horanyi, Donald D Lorimer, Thomas E Edwards, Jan Abendroth
Thiamine monophosphate kinase (ThiL) catalyzes the last step of thiamine pyrophosphate (TPP) synthesis, the ATP-dependent phosphorylation of thiamine monophosphate (TMP) to thiamine pyrophosphate. We solved the structure of ThiL from the human pathogen A. baumanii in complex with a pair of substrates TMP and a non-hydrolyzable adenosine triphosphate analog, and in complex with a pair of products TPP and adenosine diphosphate. High resolution of the data and anomalous diffraction allows for a detailed description of the binding mode of substrates and products, and their metal environment...
March 13, 2019: Scientific Reports
Dongbo Cai, Jiang Zhu, Shan Zhu, Yu Lu, Bowen Zhang, Kai Lu, Junhui Li, Xin Ma, Shouwen Chen
Primary metabolism plays a key role in the synthesis of secondary metabolite. In this study, the main transcription factors in carbon, nitrogen and phosphorus metabolisms (CcpA, CcpC, CcpN, CodY, TnrA, GlnR and PhoP) were engineered to improve bacitracin yield in B. licheniformis DW2, an industrial strain for bacitracin production. Firstly, our results demonstrated that deletions of ccpC and ccpN improved ATP and NADPH supplies, and the bacitracin yields were respectively increased by 14.02% and 16.06% compared with that of DW2, while, it was decreased significantly in ccpA deficient strain DW2△ccpA...
March 13, 2019: ACS Synthetic Biology
Benoît Pinson, Johanna Ceschin, Christelle Saint-Marc, Bertrand Daignan-Fornier
Metabolism is a highly integrated process resulting in energy and biomass production. While individual metabolic routes are well characterized, the mechanisms ensuring crosstalk between pathways are poorly described though they are crucial for homeostasis. Here, we establish a co-regulation of purine and pyridine metabolism in response to external adenine through two separable mechanisms. First, adenine depletion promotes transcriptional up-regulation of the de novo NAD+ biosynthesis genes by a mechanism requiring the key-purine intermediates ZMP/SZMP and the Bas1/Pho2 transcription factors...
March 12, 2019: ELife
Xuan Teng, Mingsheng Zhong, Xiaopin Zhu, Chunming Wang, Yulong Ren, Yunlong Wang, Huan Zhang, Ling Jiang, Di Wang, Yuanyuan Hao, Mingming Wu, Jianping Zhu, Xin Zhang, Xiuping Guo, Yihua Wang, Jianmin Wan
Starch is the most important form of energy storage in cereal crops. Many key enzymes involved in starch biosynthesis have been identified. However, the molecular mechanisms underlying the regulation of starch biosynthesis are largely unknown. In this study, we isolated a novel floury endosperm rice (Oryza sativa) mutant flo16 with defective starch grain (SG) formation. The amylose content and amylopectin structure were both altered in the flo16 mutant. Map-based cloning and complementation tests demonstrated that FLO16 encodes a NAD-dependent cytosolic malate dehydrogenase (CMDH)...
March 12, 2019: Plant Biotechnology Journal
Zhengshan Luo, Weizhu Zeng, Guocheng Du, Jian Chen, Jingwen Zhou
Energy metabolism plays an important role in the growth and central metabolic pathways of cells. Manipulating energy metabolism is an efficient strategy to improve the formation of target products and to understand the effects of altering intracellular energy levels on global metabolic networks. </i>Candida glabrata<i>, as a dominant yeast strain for producing pyruvate, principally converts glucose to pyruvate through the glycolytic pathway. However, this process can be severely inhibited by a high intracellular ATP content...
March 11, 2019: ACS Synthetic Biology
Jess Rhee, Lauren A Solomon, Rodney P DeKoter
Differentiation of myeloid progenitor cells into macrophages is accompanied by increased PU.1 concentration and increasing cell cycle length, culminating in cell cycle arrest. Induction of PU.1 expression in a cultured myeloid cell line expressing low PU.1 concentration results in decreased levels of mRNA encoding ATP-Citrate Lyase (ACL) and cell cycle arrest. ACL is an essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. We hypothesized that ACL may play a role in cell cycle regulation in the myeloid lineage...
March 1, 2019: Blood Cells, Molecules & Diseases
Marie Charlotte Schoelmerich, Volker Müller
The ancient reductive acetyl-CoA pathway is employed by acetogenic bacteria to form acetate from inorganic energy sources. Since the central pathway does not gain net ATP by substrate-level phosphorylation, chemolithoautotrophic growth relies on the additional formation of ATP via a chemiosmotic mechanism. Genome analyses indicated that some acetogens only have an energy-converting, ion-translocating hydrogenase (Ech) as a potential respiratory enzyme. Although the Ech-encoding genes are widely distributed in nature, the proposed function of Ech as an ion-translocating chemiosmotic coupling site has neither been demonstrated in bacteria nor has it been demonstrated that it can be the only energetic coupling sites in microorganisms that depend on a chemiosmotic mechanism for energy conservation...
March 8, 2019: Proceedings of the National Academy of Sciences of the United States of America
Xinying Zhang, Jing Chen, Xiaoyan Liu, Mingjing Gao, Xueping Chen, Cheng Huang
PAHs affect the uptake of heavy metal by plants. The uptake pathway, distribution and detoxification of nickel (Ni) in Agropyron cristatum L. (A. cristatum) were investigated in the presence of pyrene in this study. Most of Ni was adsorbed on the cell wall in the insoluble phosphate (57.31-72.18%) form and pectate and protein integrated (38.27-38.98%) form. Ni was transferred to the organelle (from 37.84% to 40.52%) in the presence of pyrene. The concentration of Ni in A. cristatum decreased by 27.42%; it was affected by the ATP production inhibitor and 29...
March 5, 2019: Ecotoxicology and Environmental Safety
Weilan Zhang, Zhigang Yu, Pinhua Rao, Irene M C Lo
Information on the environmental impact of magnetic TiO2 -based nanophotocatalysts is scarce. This study evaluated the potential effects of an innovative magnetic nanophotocatalyst N-TiO2 /Fe3 O4 @SiO2 (NTFS) on plants using Arabidopsis thaliana grown in a hydroponic system. NTFS was detected in the vascular tissues and mesophyll of plants, thus confirming the uptake and upwards transport of NTFS from roots to leaves. Fourier transform infrared spectroscopy was applied to determine compositional and structural alterations in plant tissues exposed to NTFS, or its two main components (N-TiO2 and Fe3 O4 @SiO2 ), at concentrations ranging from 0 to 1000 mg/L, but no changes were detected in the lipids, pectins, proteins, cellulose, hemicellulose, and carbohydrates...
February 28, 2019: Chemosphere
Niki Abbasi, Maryam Navi, Janine K Nunes, Scott S H Tsai
Microparticles are used in a variety of different fields, such as drug delivery. Recently, non-spherical microparticle generation has become desirable. The high surface-to-volume ratio of non-spherical microparticles allows for enhanced targeting, and attachment to cells and tissue. Current non-spherical microparticle generation techniques require complicated setup, and utilizing natural micrograins, such as pollen grains, as non-spherical delivery vehicles, requires extensive post-processing. Here, we describe a unique and facile chemical synthesis approach, for controlled generation of pollen-like microparticles, based on ionic cross-linking of alginate and calcium chloride (CaCl2), within an all-biocompatible aqueous two-phase system (ATPS) of dextran (DEX) and polyethylene glycol (PEG)...
March 8, 2019: Soft Matter
James McClory, Gui-Xiang Hu, Jian-Wei Zou, David J Timson, Meilan Huang
In microorganisms and plants, NAGK N-acetyl-L-glutamate kinase (NAGK) catalyses the second step in L-arginine synthesis, the phosphorylation of N-Acetyl-L-glutamate (NAG) to give N-acetyl-L-glutamate-5-phosphate (NAGP). NAGK is only present in microorganisms and plants but absent from mammals, which makes it an attractive target for antimicrobial or biocidal development. Understanding the substrate binding mode and reaction mechanism of NAGK is crucial for targeting the kinase to develop potential therapies...
March 8, 2019: Journal of Physical Chemistry. B
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