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Atp citrate lyase

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https://www.readbyqxmd.com/read/28777081/binding-of-hydroxycitrate-to-human-atp-citrate-lyase
#1
Jinhong Hu, Aruna Komakula, Marie E Fraser
Hydroxycitrate from the fruit of Garcinia cambogia [i.e. (2S,3S)-2-hydroxycitrate] is the best-known inhibitor of ATP-citrate lyase. Well diffracting crystals showing how the inhibitor binds to human ATP-citrate lyase were grown by modifying the protein. The protein was modified by introducing cleavage sites for Tobacco etch virus protease on either side of a disordered linker. The protein crystallized consisted of residues 2-425-ENLYFQ and S-488-810 of human ATP-citrate lyase. (2S,3S)-2-Hydroxycitrate binds in the same orientation as citrate, but the citrate-binding domain (residues 248-421) adopts a different orientation with respect to the rest of the protein (residues 4-247, 490-746 and 748-809) from that previously seen...
August 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28727056/effects-of-protein-and-fat-concentration-in-coproduct-based-growing-calf-diets-on-adipogenic-and-lipogenic-gene-expression-blood-metabolites-and-carcass-composition
#2
J R Segers, J J Loor, S J Moisá, D Gonzalez, D W Shike
Crossbred calves ( = 30; age = 95 ± 1.7 d; BW = 179 ± 18 kg) were fed 1 of 5 growing diets: 1) corn-based control, 2) low-fat, low-protein coproduct blend, 3) high-fat, low-protein coproduct blend, 4) low-fat, high-protein coproduct blend, and 5) high-fat, high-protein coproduct blend for 112 d (growing phase) followed by a common corn-based finishing diet (additional 112 d; finishing phase). Calves were biopsied at 0, 112, and 224 d for transcriptional analysis via real-time quantitative PCR of 14 genes associated with adipogenesis and lipogenesis within the muscle...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28689661/nuclear-acetyl-coa-production-by-acly-promotes-homologous-recombination
#3
Sharanya Sivanand, Seth Rhoades, Qinqin Jiang, Joyce V Lee, Joseph Benci, Jingwen Zhang, Salina Yuan, Isabella Viney, Steven Zhao, Alessandro Carrer, Michael J Bennett, Andy J Minn, Aalim M Weljie, Roger A Greenberg, Kathryn E Wellen
While maintaining the integrity of the genome and sustaining bioenergetics are both fundamental functions of the cell, potential crosstalk between metabolic and DNA repair pathways is poorly understood. Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of histone acetylation during the DNA damage response. In this study, we report that nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28679948/prl2-links-magnesium-flux-and-sex-dependent-circadian-metabolic-rhythms
#4
Noriko Uetani, Serge Hardy, Simon-Pierre Gravel, Silke Kiessling, Adam Pietrobon, Nau Nau Wong, Valérie Chénard, Nicolas Cermakian, Julie St-Pierre, Michel L Tremblay
Magnesium (Mg2+) plays pleiotropic roles in cellular biology, and it is essentially required for all living organisms. Although previous studies demonstrated intracellular Mg2+ levels were regulated by the complex of phosphatase of regenerating liver 2 (PRL2) and Mg2+ transporter of cyclin M (CNNMs), physiological functions of PRL2 in whole animals remain unclear. Interestingly, Mg2+ was recently identified as a regulator of circadian rhythm-dependent metabolism; however, no mechanism was found to explain the clock-dependent Mg2+ oscillation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28655760/silencing-of-solute-carrier-family-13-member-5-disrupts-energy-homeostasis-and-inhibits-proliferation-of-human-hepatocarcinoma-cells
#5
Zhihui Li, Daochuan Li, Eun Yong Choi, Rena Lapidus, Lei Zhang, Shiew-Mei Huang, Paul Shapiro, Hongbing Wang
The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter, plays a key role in importing citrate from the circulation into liver cells. Recent evidence has revealed that SLC13A5 deletion protects mice from high-fat diet-induced hepatic steatosis and that mutation of the SLC13A5 orthologues in D. melanogaster and C. elegans promotes longevity. However, despite the emerging importance of SLC13A5 in energy homeostasis, whether perturbation of SLC13A5 affects the metabolism and malignancy of hepatocellular carcinoma is unknown...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#6
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
BACKGROUND & AIMS: We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS: We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses...
June 22, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28637447/differential-gene-expression-at-different-stages-of-mesocarp-development-in-high-and-low-yielding-oil-palm
#7
Yick Ching Wong, Huey Fang Teh, Katharina Mebus, Tony Eng Keong Ooi, Qi Bin Kwong, Ka Loo Koo, Chuang Kee Ong, Sean Mayes, Fook Tim Chew, David R Appleton, Harikrishna Kulaveerasingam
BACKGROUND: The oil yield trait of oil palm is expected to involve multiple genes, environmental influences and interactions. Many of the underlying mechanisms that contribute to oil yield are still poorly understood. In this study, we used a microarray approach to study the gene expression profiles of mesocarp tissue at different developmental stages, comparing genetically related high- and low- oil yielding palms to identify genes that contributed to the higher oil-yielding palm and might contribute to the wider genetic improvement of oil palm breeding populations...
June 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28550409/lipid-droplets-accumulation-and-other-biochemical-changes-induced-in-the-fungal-pathogen-ustilago-maydis-under-nitrogen-starvation
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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