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ATP-citrate lyase

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https://www.readbyqxmd.com/read/28550409/lipid-droplets-accumulation-and-other-biochemical-changes-induced-in-the-fungal-pathogen-ustilago-maydis-under-nitrogen-starvation
#1
Lucero Romero Aguilar, Juan Pablo Pardo, Mónica Montero Lomelí, Oscar Ivan Luqueño Bocardo, Marco A Juárez Oropeza, Guadalupe Guerra Sánchez
In many organisms, the growth under nitrogen-deprivation or a poor nitrogen source impacts on the carbon flow distribution and causes accumulation of neutral lipids, which are stored as lipid droplets (LDs). Efforts are in progress to find the mechanism of LDs synthesis and degradation, and new organisms capable of accumulating large amounts of lipids for biotechnological applications. In this context, when Ustilago maydis was cultured in the absence of a nitrogen source, there was a large accumulation of lipid bodies containing mainly triacylglycerols...
May 26, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28532507/isoprenoid-biosynthesis-in-dandelion-latex-is-enhanced-by-the-overexpression-of-three-key-enzymes-involved-in-the-mevalonate-pathway
#2
Katharina M Pütter, Nicole van Deenen, Kristina Unland, Dirk Prüfer, Christian Schulze Gronover
BACKGROUND: Latex from the dandelion species Taraxacum brevicorniculatum contains many high-value isoprenoid end products, e.g. triterpenes and polyisoprenes such as natural rubber. The isopentenyl pyrophosphate units required as precursors for these isoprenoids are provided by the mevalonate (MVA) pathway. The key enzyme in this pathway is 3-hydroxy-methyl-glutaryl-CoA reductase (HMGR) and its activity has been thoroughly characterized in many plant species including dandelion. However, two enzymes acting upstream of HMGR have not been characterized in dandelion latex: ATP citrate lyase (ACL), which provides the acetyl-CoA utilized in the MVA pathway, and acetoacetyl-CoA thiolase (AACT), which catalyzes the first step in the pathway to produce acetoacetyl-CoA...
May 22, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28490526/atp-citrate-lyase-is-essential-for-high-glucose-induced-histone-hyperacetylation-and-fibrogenic-gene-up-regulation-in-mesangial-cells
#3
Dilip K Deb, Yinyin Chen, Jian Sun, Youli Wang, Yan Chun Li
TThe goal of this study was to address the role of ATP-citrate lyase (ACL), an enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone acetylation and pro-fibrotic gene expression. Our recent ChIP-Seq studies have demonstrated that HG induces genome-wide histone hyperacetylation in mesangial cells (MCs). Here we showed that exposure of MCs to HG markedly increased histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of potent pro-fibrotic factors TGF-β1, TGF-β3 and CTGF...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28443474/atp-citrate-lyase-is-increased-in-human-breast-cancer-depletion-of-which-promotes-apoptosis
#4
Diyu Wang, Lei Yin, Jinrong Wei, Zhixue Yang, Guoqin Jiang
Breast cancer is a malignant tumor that is harmful to women's health around the world. Investigating the biological mechanism is, therefore, of pivotal importance to improve patients' prognoses. Compared to non-neoplastic tissues, enhanced glucose and lipid metabolism is one of the most common properties of malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key enzyme linking aerobic glycolysis and fatty acid synthesis and is of high biological and prognostic significance in breast cancer...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28433582/effects-of-twenty-standard-amino-acids-on-biochemical-constituents-docosahexaenoic-acid-production-and-metabolic-activity-changes-of-crypthecodinium-cohnii
#5
Waseem Safdar, Xinyi Zan, Muhammad Shamoon, Hafiz Rizwan Sharif, Omar Mukama, Xin Tang, Yuanda Song
The influence of 20 standard amino acids was investigated on growth, lipid accumulation, docosahexaenoic acid (DHA) production and cell biochemical composition of Crypthecodinium cohnii. C. cohnii efficiently utilize organic nitrogen (predominantly threonine and to a lesser extent tyrosine and serine) as compared to inorganic nitrogen (NH4)2SO4. However, No significant effect was observed on major biochemical composition of C. cohnii (lipids, carbohydrates and proteins) under N limitation or supplementation with different N-sources...
August 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28429330/growth-kinetics-fatty-acid-composition-and-metabolic-activity-changes-of-crypthecodinium-cohnii-under-different-nitrogen-source-and-concentration
#6
Waseem Safdar, Muhammad Shamoon, Xinyi Zan, Junaid Haider, Hafiz Rizwan Sharif, Muhammad Shoaib, Yuanda Song
The effect of varying concentrations of the nitrogen source on the growth kinetics, lipid accumulation, lipid and DHA productivity, and fatty acid composition of C. cohnii was elucidated. Growth of C. cohnii was in three distinct growth stages: cell growth, lipid accumulation and a final lipid turnover stage. Most of lipids were accumulated in lipid accumulation stage (48-120 h) though, slow growth rate was observed during this stage. NaNO3 supported significantly higher lipid content (26.9% of DCW), DHA content (0...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28407230/acyl-coa-synthetase-short-chain-family-member-2-acss2-is-regulated-by-srebp-1-and-plays-a-role-in-fatty-acid-synthesis-in-caprine-mammary-epithelial-cells
#7
Huifen Xu, Jun Luo, Gongzhen Ma, Xueying Zhang, Dawei Yao, Ming Li, Juan J Loor
Sterol regulatory element binding protein 1 (SREBP-1) is well-known as the master regulator of lipogenesis in rodents. Acyl-CoA synthetase short-chain family member 2 (ACSS2) plays a key role in lipogenesis by synthesizing acetyl-CoA from acetate for lipogenesis. ATP citrate lyase (ACLY) catalyzes the conversion of citrate and coenzyme A to acetyl-CoA, hence, it is also important for lipogenesis. Although ACSS2 function in cancer cells has been elucidated, its essentiality in ruminant mammary lipogenesis is unknown...
April 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28357621/improved-campesterol-production-in-engineered-yarrowia-lipolytica-strains
#8
Yu Zhang, Ying Wang, Mingdong Yao, Hong Liu, Xiao Zhou, Wenhai Xiao, Yingjin Yuan
OBJECTIVES: To engineer Yarrowia lipolytica for improving the heterologous production of campesterol (a key precursor to manufacture pharmaceutical steroids). RESULTS: By screening 7-dehydrocholesterol reductase (DHCR7) from diverse species, DHCR7 from Danio rerio was the best candidate for campesterol synthesis. Overexpression of ACL (ATP: citrate lyase) or POX2 (peroxisome acyl-CoA oxidase 2) were key to improving campesterol production. The highest yield of campesterol was 942 mg/l was with the strain overexpressing POX2 in a 5 l bioreactor via high cell density fermentation process with a restricted supply of carbon sourc, sunflower seed oil...
March 29, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28298542/lipid-emulsion-added-to-a-liquid-high-carbohydrate-diet-and-voluntary-running-exercise-reduce-lipogenesis-and-ameliorate-early-stage-hepatic-steatosis-in-mice
#9
Kuan-Hsun Huang, Lei Hao, Philip B Smith, Connie J Rogers, Andrew D Patterson, A Catharine Ross
Background: The use of parenteral nutrition formulas is often associated with the development of hepatic steatosis. We have shown previously that the addition of a lipid emulsion (LE) rich in n-6 (ω-6) fatty acids (FAs) ameliorated triglyceride (TG) accumulation in the livers of nonobese mice fed a high-carbohydrate diet (HCD) for 5 wk. However, it remains unclear how rapidly this condition develops and whether it can be prevented by LE with or without a running wheel for voluntary exercise (Exe).Objective: We investigated in an 8-d study whether mice develop steatosis and whether the administration of LE with or without Exe reduces the concentration of total FAs and prevents an increase in the expression of genes in the liver associated with lipogenesis...
May 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#10
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28167750/acss2-mediated-acetyl-coa-synthesis-from-acetate-is-necessary-for-human-cytomegalovirus-infection
#11
Anna Vysochan, Arjun Sengupta, Aalim M Weljie, James C Alwine, Yongjun Yu
Recent studies have shown that human cytomegalovirus (HCMV) can induce a robust increase in lipid synthesis which is critical for the success of infection. In mammalian cells the central precursor for lipid biosynthesis, cytosolic acetyl CoA (Ac-CoA), is produced by ATP-citrate lyase (ACLY) from mitochondria-derived citrate or by acetyl-CoA synthetase short-chain family member 2 (ACSS2) from acetate. It has been reported that ACLY is the primary enzyme involved in making cytosolic Ac-CoA in cells with abundant nutrients...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28153881/prevention-of-diet-induced-metabolic-dysregulation-inflammation-and-atherosclerosis-in-ldlr-mice-by-treatment-with-the-atp-citrate-lyase-inhibitor-bempedoic-acid
#12
Joshua P Samsoondar, Amy C Burke, Brian G Sutherland, Dawn E Telford, Cynthia G Sawyez, Jane Y Edwards, Stephen L Pinkosky, Roger S Newton, Murray W Huff
OBJECTIVE: Bempedoic acid (ETC-1002, 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel low-density lipoprotein cholesterol-lowering compound. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis...
April 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28129980/discovery-of-furan-carboxylate-derivatives-as-novel-inhibitors-of-atp-citrate-lyase-via-virtual-high-throughput-screening
#13
Finith E Jernigan, Jun-Ichi Hanai, Vikas P Sukhatme, Lijun Sun
The enzyme ATP citrate lyase (ACL) catalyzes the formation of cytosolic acetyl CoA, the starting material for de novo lipid and cholesterol biosynthesis. The dysfunction and upregulation of ACL in numerous cancers makes it an attractive target for developing anticancer therapies. ACL inhibition by shRNA knockdown limits cancer cell proliferation and reduces cancer stemness. We designed and implemented a dual docking protocol to select virtual ACL inhibitors that were scored among the top 10 percentiles by both the Autodock Vina and the Glamdock algorithms...
January 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28106122/comparative-genomics-and-transcriptome-analysis-of-aspergillus-niger-and-metabolic-engineering-for-citrate-production
#14
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains-namely, A. niger H915-1 (citrate titer: 157 g L(-1)), A1 (117 g L(-1)), and L2 (76 g L(-1))-to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078050/complete-genome-sequence-of-lutibacter-profundi-lp1-t-isolated-from-an-arctic-deep-sea-hydrothermal-vent-system
#15
Juliane Wissuwa, Sven Le Moine Bauer, Ida Helene Steen, Runar Stokke
Lutibacter profundi LP1(T) within the family Flavobacteriaceae was isolated from a biofilm growing on the surface of a black smoker chimney at the Loki's Castle vent field, located on the Arctic Mid-Ocean Ridge. The complete genome of L. profundi LP1(T) is the first genome to be published within the genus Lutibacter. L. profundi LP1(T) consists of a single 2,966,978 bp circular chromosome with a GC content of 29.8%. The genome comprises 2,537 protein-coding genes, 40 tRNA species and 2 rRNA operons. The microaerophilic, organotrophic isolate contains genes for all central carbohydrate metabolic pathways...
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/28077572/impact-of-a-high-fat-diet-on-tissue-acyl-coa-and-histone-acetylation-levels
#16
Alessandro Carrer, Joshua L D Parris, Sophie Trefely, Ryan A Henry, David C Montgomery, AnnMarie Torres, John M Viola, Yin-Ming Kuo, Ian A Blair, Jordan L Meier, Andrew J Andrews, Nathaniel W Snyder, Kathryn E Wellen
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28059952/atp-citrate-lyase-genetics-molecular-biology-and-therapeutic-target-for-dyslipidemia
#17
Amy C Burke, Murray W Huff
PURPOSE OF REVIEW: ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition. RECENT FINDINGS: ACLY is a critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis. Human genetic variants have been associated with enhanced growth and survival of several cancers, and with attenuated plasma triglyceride responses to dietary fish oil...
April 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28018484/mechanistic-insights-into-the-effect-of-imidazolium-ionic-liquid-on-lipid-production-by-geotrichum-fermentans
#18
Li-Ping Liu, Min-Hua Zong, Robert J Linhardt, Wen-Yong Lou, Ning Li, Chao Huang, Hong Wu
BACKGROUND: Ionic liquid (IL) pretreatment has emerged as a promising technique that enables complete utilization of lignocellulosic biomass for biofuel production. However, imidazolium IL has recently been shown to exhibit inhibitory effect on cell growth and product formation of industrial microbes, such as oleaginous microorganisms. To date, the mechanism of this inhibition remains largely unknown. RESULTS: In this study, the feasibility of [Bmim][OAc]-pretreated rice straw hydrolysate as a substrate for microbial lipid production by Geotrichum fermentans, also known as Trichosporon fermentans, was evaluated...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28018404/functional-and-integrative-analysis-of-the-proteomic-profile-of-radish-root-under-pb-exposure
#19
Yan Wang, Liang Xu, Mingjia Tang, Haiyan Jiang, Wei Chen, Wei Zhang, Ronghua Wang, Liwang Liu
Lead (Pb) is one of the most abundant heavy metal (HM) pollutants, which can penetrate the plant through the root and then enter the food chain causing potential health risks for human beings. Radish is an important root vegetable crop worldwide. To investigate the mechanism underlying plant response to Pb stress in radish, the protein profile changes of radish roots respectively upon Pb(NO3)2 at 500 mg L(-1)(Pb500) and 1000 mg L(-1)(Pb1000), were comprehensively analyzed using iTRAQ (Isobaric Tag for Relative and Absolute Quantification)...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27997879/design-and-synthesis-of-emodin-derivatives-as-novel-inhibitors-of-atp-citrate-lyase
#20
Steffi K Koerner, Jun-Ichi Hanai, Sha Bai, Finith E Jernigan, Miwa Oki, Chieko Komaba, Emi Shuto, Vikas P Sukhatme, Lijun Sun
Aberrant cellular metabolism drives cancer proliferation and metastasis. ATP citrate lyase (ACL) plays a critical role in generating cytosolic acetyl CoA, a key building block for de novo fatty acid and cholesterol biosynthesis. ACL is overexpressed in cancer cells, and siRNA knockdown of ACL limits cancer cell proliferation and reduces cancer stemness. We characterized a new class of ACL inhibitors bearing the key structural feature of the natural product emodin. Structure-activity relationship (SAR) study led to the identification of 1d as a potent lead that demonstrated dose-dependent inhibition of proliferation and cancer stemness of the A549 lung cancer cell line...
January 27, 2017: European Journal of Medicinal Chemistry
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