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Acetyl-coa synthetase

Shaojin Zhang, Juanjuan He, Zhankui Jia, Zechen Yan, Jinjian Yang
BACKGROUND: Acetyl-CoA synthetase 2 (ACSS2) is highly expressed in various cancers, whereas ACSS2 expression and function in renal cell carcinoma (RCC) are unknown. METHODS: We investigated ACSS2 expression in 198 human RCC tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. Overexpression and knockdown of ACSS2 were used to investigate the proliferation, migration and invasion of human RCC 786-O, 769-P, and ACHN cell lines...
March 1, 2018: Urologic Oncology
Wei-Chun Chang, Wei-Chung Cheng, Bi-Hua Cheng, Lumin Chen, Li-Jing Ju, Yu-Jer Ou, Long-Bin Jeng, Mei-Due Yang, Yao-Ching Hung, Wen-Lung Ma
Cholesterol affects cancer progression, and acetyl-CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl-CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan-Meier Plotter web-based gene survival analyzer and The Cancer Genome Atlas (TCGA)-database analyzed with DBdriver.v2 platform, we revealed acetyl-CoA production and the mevalonate pathway are associated with GCa prognosis...
March 1, 2018: Cancer Medicine
Yoshio Kimura, Chihiro Tanaka, Manami Oka
Myxococcus xanthus generates diadenosine tetraphosphates (Ap4 A) and diadenosine pentaphosphates (Ap5 A) under various stress conditions. M. xanthus lysyl-tRNA synthetase (LysS) efficiently synthesizes Ap4 A from ATP, Ap5 A from ATP and adenosine tetraphosphate (Ap4 ), and Ap4 from ATP and triphosphate. To identify other M. xanthus enzymes that can catalyze Ap4 A and Ap4 synthesis, 15 M. xanthus aminoacyl-tRNA synthetases (aaRSs), four acyl-CoA synthetases (Acys), three acetyl-CoA synthetases (Aces), phosphoglycerate kinase (Pgk), and adenylate kinase (Adk) were expressed in Escherichia coli and examined for Ap4 A or Ap4 synthetase activity using ATP or ATP and triphosphate as substrates...
February 21, 2018: Current Microbiology
E Ren, X Chen, S Yu, J Xu, Y Su, W Zhu
Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body's metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group...
February 20, 2018: Animal: An International Journal of Animal Bioscience
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
Daniel Camara Teixeira, Elizabeth L Cordonier, Subhashinee S K Wijeratne, Patricia Huebbe, Augusta Jamin, Sarah Jarecke, Matthew Wiebe, Janos Zempleni
The mitochondrial proteome comprises 1000 to 1500 proteins, in addition to proteins for which the mitochondrial localization is uncertain. About 800 diseases have been linked with mutations in mitochondrial proteins. We devised a cell survival assay for assessing the mitochondrial localization in a high-throughput format. This protocol allows us to assess the mitochondrial localization of proteins and their mutants, and to identify drugs and nutrients that modulate the mitochondrial targeting of proteins. The assay works equally well for proteins directed to the outer mitochondrial membrane, inner mitochondrial membrane mitochondrial and mitochondrial matrix, as demonstrated by assessing the mitochondrial targeting of the following proteins: carnitine palmitoyl transferase 1 (consensus sequence and R123C mutant), acetyl-CoA carboxylase 2, uncoupling protein 1 and holocarboxylase synthetase...
January 31, 2018: Journal of Nutritional Biochemistry
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
Mariane T de Paula, Márcia R P Silva, Stífani M Araújo, Vandreza C Bortolotto, Illana K Martins, Giulianna E Macedo, Jeferson L Franco, Thaís Posser, Marina Prigol
Maternal obesity and metabolic diseases are two of the most important potential dangers to offspring, given that impaired offspring may cause deficiencies that impair the adult life and health. This study evaluated the oxidative damage, the enzymatic antioxidant defenses, and the enzymes of fatty acid metabolism, such as Acyl-CoA Synthetase and Acetyl-CoA Synthetase (mRNA expression levels), as well as the modulation of cell stress signaling pathway, as Hsp83, and gene expression and insulin-like peptide DILP6 in Drosophila melanogaster models that received a high fat diet (HFD) (10% and 20% of coconut oil) throughout their development period...
January 29, 2018: Journal of Cellular Biochemistry
Tsubasa Fuke, Takaaki Sato, Savyasachee Jha, Myra L Tansengco, Haruyuki Atomi
Phytoene (C40H64) is an isoprenoid and a precursor of various carotenoids which are of industrial value. Archaea can be considered to exhibit a relatively large capacity to produce isoprenoids, as they are components of their membrane lipids. Here, we aimed to produce isoprenoids such as phytoene in the hyperthermophilic archaeon Thermococcus kodakarensis. T. kodakarensis harbors a prenyltransferase gene involved in the biosynthesis of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are precursors of squalene and phytoene, respectively...
January 16, 2018: Extremophiles: Life Under Extreme Conditions
Cecilie Morland, Anne-Sofie Frøland, Mi Nyguyen Pettersen, Jon Storm-Mathisen, Vidar Gundersen, Frode Rise, Bjørnar Hassel
Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in striatum and neocortex...
January 16, 2018: Biochemical Journal
Udhayakumar Gopal, Salvatore V Pizzo
Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signals through tumor Cell Surface GRP78 (CS-GRP78) to regulate tumor cell proliferation through multiple signaling pathway. Here, we demonstrate that the α2M*/CS-GRP78 axis regulates acetyl-CoA synthesis and thus functions as an epigenetic modulator by enhancing histone acetylation in cancer cells...
December 8, 2017: Oncotarget
Rui Chen, Min Xu, Jason Nagati, Joseph A Garcia
Survival of cancer cells in the harsh tumor microenvironment, characterized by oxygen and glucose deprivation, requires rapid initiation of cytoprotective measures. Metabolites whose levels change during stress are ideal signaling cues, particularly if used in post-translational modifications of stress-responsive signal transducers. In cancer cells exposed to oxygen or glucose deprivation, there is an increase in cellular levels of acetate, a substrate for acetate-dependent acetyl CoA synthetase 2 (Acss2) that also stimulates translocation of Acss2 from the cytosol to the nucleus...
2017: PloS One
Bhesh Raj Sharma, Hyun Jung Kim, Min Suk Kim, Chul Min Park, Dong Young Rhyu
Seaweeds are considered a potential source of antiobesity agents. Because Caulerpa, a seaweed, has been consumed for food in Japan, China, South Korea, and Australia, we hypothesized that Caulerpa okamurae may have antiobesity effects in an animal model of high-fat diet (HFD)-induced obesity in C57BL/6 mice. Herein, we found that the ethanolic extract of C okamurae (COE) significantly inhibited lipid accumulation and reduced the expression of the master regulator of adipogenesis, peroxisome proliferator-activated receptor-γ, sterol regulatory element binding protein-1c, and CCAAT/enhancer-binding protein-α in 3T3-L1 adipocytes...
November 2017: Nutrition Research
Masaya Shimada, Masato Hibino, Anna Takeshita
Excessive fructose ingestion drastically enhances hepatic lipid accumulation. The most prominent form of inositol-myo-inositol (MI)-remarkably reduces high sucrose-induced hepatic triglyceride (TG) accumulation. Because MI is a major and strong lipotrope, we hypothesized in this study that MI improves fatty liver more induced by excessive ingestion of fructose than sucrose. Rats were fed a high-glucose diet (HGD), a high-fructose diet (HFD), or an HFD supplemented with 0.2% MI for 12 days. Hepatic levels of TG and mRNAs for fructolysis (ketohexokinase and aldolase B), lipogenesis (pyruvate kinase, liver, and RBC; glucose-6-phosphate dehydrogenase; acetyl-CoA carboxylase alpha; fatty acid synthase; and stearoyl-CoA desaturase 1), and a key transcription factor for lipogenesis-carbohydrate-responsive element-binding protein-were significantly increased in the HFD group compared with the HGD group, and the increase was markedly decreased by MI supplementation...
November 2017: Nutrition Research
Shinya Hasegawa, Masahiko Imai, Masahiro Yamasaki, Noriko Takahashi, Tetsuya Fukui
Acetoacetyl-CoA synthetase (AACS) is the enzyme responsible for cholesterol and fatty acid synthesis in the cytosol. We have previously shown that AACS has an important role in normal neuronal development and that knockdown of SREBP-2, which orchestrates cholesterol synthesis, resulted in the downregulation of AACS mRNA levels. In this study, we investigated the transcriptional mechanism of AACS in Neuro-2a, neuroblastoma cells. Luciferase assay showed that the minimal core promoter of the mouse AACS gene is located in a region with 110 bps upstream from the transcription start site...
January 1, 2018: Biochemical and Biophysical Research Communications
Yi-Hsiu Chung, Cheng-Kun Tsai, Chiun-Chieh Wang, Hsi-Mu Chen, Kuan-Ying Lu, Han Chiu, Yu-Chun Lin, Tzu-Chen Yen, Gigin Lin
We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and [(11)C]acetate ([(11)C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [(18)F]FDG and [(11)C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR...
November 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Junjun Wu, Xia Zhang, Peng Zhou, Jiaying Huang, Xiudong Xia, Wei Li, Ziyu Zhou, Yue Chen, Yinghao Liu, Mingsheng Dong
Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C6 -C10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield...
November 2017: Metabolic Engineering
Miao-Miao Wang, Di You, Bang-Ce Ye
Reversible N(ε)-lysine acetylation has emerging as an important metabolic regulatory mechanism in microorganisms. Herein, we systematically investigated the site-specific and kinetic characterization of enzymatic (lysine acetyltransferase) and nonenzymatic acetylation (AcP-dependent or Acyl-CoA-dependent), as well as their different effect on activity of metabolic enzyme (AMP-forming acetyl-CoA synthetase, Acs). It was found that Bacillus subtilis acetyl-CoA synthetase (BsAcsA) can be acetylated in vitro either catalytically by lysine acetyltransferase BsAcuA and Ac-CoA (at low concentration), or nonenzymatically by Ac-CoA or AcP (at high concentration)...
November 1, 2017: Scientific Reports
Zhuo Chen, Ling Luo, Runfa Chen, Hanhua Hu, Yufang Pan, Haibo Jiang, Xia Wan, Hu Jin, Yangmin Gong
N(ε) -lysine acetylation represents a highly dynamic and reversibly regulated post-translational modification widespread in almost all organisms, and plays important roles for regulation of protein function in diverse metabolic pathways. However, little is known about the role of lysine acetylation in photosynthetic eukaryotic microalgae. We integrated proteomic approaches to comprehensively characterize the lysine acetylome in the model diatom Phaeodactylum tricornutum. In total, 2324 acetylation sites from 1220 acetylated proteins were identified, representing the largest dataset of the lysine acetylome in plants to date...
November 1, 2017: Molecular & Cellular Proteomics: MCP
Geoffray Monteuuis, Fumi Suomi, Juha M Kerätär, Ali J Masud, Alexander J Kastaniotis
Mitochondrial fatty acid synthesis (mtFAS) is a highly conserved pathway essential for mitochondrial biogenesis. The mtFAS process is required for mitochondrial respiratory chain assembly and function, synthesis of the lipoic acid cofactor indispensable for the function of several mitochondrial enzyme complexes and essential for embryonic development in mice. Mutations in human mtFAS have been reported to lead to neurodegenerative disease. The source of malonyl-CoA for mtFAS in mammals has remained unclear...
November 6, 2017: Biochemical Journal
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