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Acetyl-CoA

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https://www.readbyqxmd.com/read/28092657/lipid-production-in-yarrowia-lipolytica-is-maximized-by-engineering-cytosolic-redox-metabolism
#1
Kangjian Qiao, Thomas M Wasylenko, Kang Zhou, Peng Xu, Gregory Stephanopoulos
Microbial factories have been engineered to produce lipids from carbohydrate feedstocks for production of biofuels and oleochemicals. However, even the best yields obtained to date are insufficient for commercial lipid production. To maximize the capture of electrons generated from substrate catabolism and thus increase substrate-to-product yields, we engineered 13 strains of Yarrowia lipolytica with synthetic pathways converting glycolytic NADH into the lipid biosynthetic precursors NADPH or acetyl-CoA. A quantitative model was established and identified the yield of the lipid pathway as a crucial determinant of overall process yield...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#2
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088260/korean-chungtaejeon-tea-extract-attenuates-body-weight-gain-in-c57bl-6j-lep-ob-ob-mice-and-regulates-adipogenesis-and-lipolysis-in-3t3-l1-adipocytes
#3
Bhesh Raj Sharma, Dong Wook Kim, Dong Young Rhyu
OBJECTIVE: Traditional Korean Chungtaejeon (CTJ) tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS: The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses...
January 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28081360/pinus-densiflora-bark-extract-pinexol-decreased-adiposity-in-mice-by-down-regulation-of-hepatic-de-novo-lipogenesis-and-adipogenesis-in-white-adipose-tissue
#4
Hyemyoung Ahn, Gwang-Woong Go
PineXol, extracted from Korean red pine bark, has beneficial effects, such as antioxidant, anti3 inflammatory, and anti-lipogenic activities in vitro. We tested the hypothesis that PineXol supplementation could have anti-obesity effects on mice fed a high-fat diet (HFD). Four-week old male C57BL/6 mice were fed normal chow (18% kcal from fat) or HFD (60% kcal from fat). HFD-fed animals were also subjected to PineXol treatment at a dose of 10 or 50 mg/kg body weight (BW) (PX10 or PX50, respectively) body weight...
January 12, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28081256/inhibition-of-acetyl-coa-carboxylase-1-acc1-and-2-acc2-reduces-proliferation-and-de-novo-lipogenesis-of-egfrviii-human-glioblastoma-cells
#5
Jessica E C Jones, William P Esler, Rushi Patel, Adhiraj Lanba, Nicholas B Vera, Jeffrey A Pfefferkorn, Cecile Vernochet
Tumor cell proliferation and migration processes are regulated by multiple metabolic pathways including glycolysis and de novo lipogenesis. Since acetyl-CoA carboxylase (ACC) is at the junction of lipids synthesis and oxidative metabolic pathways, we investigated whether use of a dual ACC inhibitor would provide a potential therapy against certain lipogenic cancers. The impact of dual ACC1/ACC2 inhibition was investigated using a dual ACC1/ACC2 inhibitor as well as dual siRNA knock down on the cellular viability and metabolism of two glioblastoma multiform cancer cell lines, U87 and a more aggressive form, U87 EGFRvIII...
2017: PloS One
https://www.readbyqxmd.com/read/28078675/overexpression-of-a-diacylglycerol-acyltransferase-gene-in-phaeodactylum-tricornutum-directs-carbon-towards-lipid-biosynthesis
#6
Jorge Dinamarca, Orly Levitan, G K Kumaraswamy, Desmond S Lun, Paul Falkowski
Under nutrient deplete conditions, diatoms accumulate between 15 to 25% of their dry weight as lipids, primarily as triacylglycerols (TAGs). As in most eukaryotes, these organisms produce TAGs via the acyl-CoA dependent Kennedy pathway. The last step in this pathway is catalyzed by diacylglycerol acyltransferase (DGAT) that acylates diacylglycerol (DAG) to produce TAG. To test our hypothesis that DGAT plays a major role in controlling the flux of carbon towards lipids, we overexpressed a specific type II DGAT gene, DGAT2D, in the model diatom Phaeodactylum tricornutum...
January 12, 2017: Journal of Phycology
https://www.readbyqxmd.com/read/28078513/determining-the-roles-of-the-three-alcohol-dehydrogenases-adha-adhb-and-adhe-in-thermoanaerobacter-ethanolicus-during-ethanol-formation
#7
Jilai Zhou, Xiongjun Shao, Daniel G Olson, Sean Jean-Loup Murphy, Liang Tian, Lee R Lynd
Thermoanaerobacter ethanolicus is a promising candidate for biofuel production due to the broad range of substrates it can utilize and its high ethanol yield compared to other thermophilic bacteria, such as Clostridium thermocellum. Three alcohol dehydrogenases, AdhA, AdhB and AdhE, play key roles in ethanol formation. To study their physiological roles during ethanol formation, we deleted them separately and in combination. Previously, it has been thought that both AdhB and AdhE were bifunctional alcohol dehydrogenases...
January 11, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28077572/impact-of-high-fat-diet-on-tissue-acyl-coa-and-histone-acetylation-levels
#8
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 (ACLY) 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 ACLY levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076367/a-chemogenomic-screen-reveals-novel-snf1p-ampk-independent-regulators-of-acetyl-coa-carboxylase
#9
Bruno L Bozaquel-Morais, Juliana B Madeira, Thiago M Venâncio, Thiago Pacheco-Rosa, Claudio A Masuda, Monica Montero-Lomeli
Acetyl-CoA carboxylase (Acc1p) is a key enzyme in fatty acid biosynthesis and is essential for cell viability. To discover new regulators of its activity, we screened a Saccharomyces cerevisiae deletion library for increased sensitivity to soraphen A, a potent Acc1p inhibitor. The hits identified in the screen (118 hits) were filtered using a chemical-phenotype map to exclude those associated with pleiotropic drug resistance. This enabled the identification of 82 ORFs that are genetic interactors of Acc1p. The main functional clusters represented by these hits were "transcriptional regulation", "protein post-translational modifications" and "lipid metabolism"...
2017: PloS One
https://www.readbyqxmd.com/read/28070695/barth-syndrome-connecting-cardiolipin-to-cardiomyopathy
#10
REVIEW
Nikita Ikon, Robert O Ryan
The Barth syndrome (BTHS) is caused by an inborn error of metabolism that manifests characteristic phenotypic features including altered mitochondrial membrane phospholipids, lactic acidosis, organic acid-uria, skeletal muscle weakness and cardiomyopathy. The underlying cause of BTHS has been definitively traced to mutations in the tafazzin (TAZ) gene locus on chromosome X. TAZ encodes a phospholipid transacylase that promotes cardiolipin acyl chain remodeling. Absence of tafazzin activity results in cardiolipin molecular species heterogeneity, increased levels of monolysocardiolipin and lower cardiolipin abundance...
January 9, 2017: Lipids
https://www.readbyqxmd.com/read/28070562/biological-and-chemical-adaptation-to-endogenous-hydrogen-peroxide-production-in-streptococcus-pneumoniae-d39
#11
John P Lisher, Ho-Ching Tiffany Tsui, Smirla Ramos-Montañez, Kristy L Hentchel, Julia E Martin, Jonathan C Trinidad, Malcolm E Winkler, David P Giedroc
The catalase-negative, facultative anaerobe Streptococcus pneumoniae D39 is naturally resistant to hydrogen peroxide (H2O2) produced endogenously by pyruvate oxidase (SpxB). Here, we investigate the adaptive response to endogenously produced H2O2. We show that lactate oxidase, which converts lactate to pyruvate, positively impacts pyruvate flux through SpxB and that ΔlctO mutants produce significantly lower H2O2. In addition, both the SpxB pathway and a candidate pyruvate dehydrogenase complex (PDHC) pathway contribute to acetyl coenzyme A (acetyl-CoA) production during aerobic growth, and the pyruvate format lyase (PFL) pathway is the major acetyl-CoA pathway during anaerobic growth...
January 2017: MSphere
https://www.readbyqxmd.com/read/28067952/plastomes-on-the-edge-the-evolutionary-breakdown-of-mycoheterotroph-plastid-genomes
#12
REVIEW
Sean W Graham, Vivienne K Y Lam, Vincent S F T Merckx
I. II. III. References SUMMARY: We examine recent evidence for ratchet-like genome degradation in mycoheterotrophs, plants that obtain nutrition from fungi. Initial loss of the NADH dehydrogenase-like (NDH) complex may often set off an irreversible evolutionary cascade of photosynthetic gene losses. Genes for plastid-encoded subunits of RNA polymerase and photosynthetic enzymes with secondary functions (Rubisco and ATP synthase) can persist initially, with nonsynchronous and quite broad windows in the relative timing of their loss...
January 9, 2017: New Phytologist
https://www.readbyqxmd.com/read/28067471/traditional-and-novel-tools-to-probe-the-mitochondrial-metabolism-in-health-and-disease
#13
REVIEW
Yanfei Zhang, José L Avalos
Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer...
January 9, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28062645/crystallographic-substrate-binding-studies-of-leishmania-mexicana-scp2-thiolase-type-2-unique-features-of-oxyanion-hole-1
#14
Rajesh K Harijan, Tiila-Riikka Kiema, Shahan M Syed, Imran Qadir, Muriel Mazet, Frédéric Bringaud, Paul A M Michels, Rik K Wierenga
Structures of the C123A variant of the dimeric Leishmania mexicana SCP2-thiolase (type-2) (Lm-thiolase), complexed with acetyl-CoA and acetoacetyl-CoA, respectively, are reported. The catalytic site of thiolase contains two oxyanion holes, OAH1 and OAH2, which are important for catalysis. The two structures reveal for the first time the hydrogen bond interactions of the CoA-thioester oxygen atom of the substrate with the hydrogen bond donors of OAH1 of a CHH-thiolase. The amino acid sequence fingerprints ( C: xS, N: EAF, G H: P) of three catalytic loops identify the active site geometry of the well-studied CNH-thiolases, whereas SCP2-thiolases (type-1, type-2) are classified as CHH-thiolases, having as corresponding fingerprints C: xS, H: DCF and G H: P...
January 5, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28062532/lipid-synthesis-is-a-metabolic-liability-of-non-small-cell-lung-cancer
#15
Robert U Svensson, Reuben J Shaw
The renaissance in the study of cancer metabolism has refocused efforts to identify and target metabolic dependencies of tumors as an approach for cancer therapy. One of the unique metabolic requirements that cancer cells possess to sustain their biosynthetic growth demands is altered fatty acid metabolism, in particular the synthesis of de novo fatty acids that are required as cellular building blocks to support cell division. Enhanced fatty acid synthesis that is observed in many tumor types has been postulated to open a therapeutic window for cancer therapy and, correspondingly, efforts to pharmacologically inhibit key enzymes of fatty acid synthesis are being pursued...
January 6, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28061812/improving-the-production-of-acetyl-coa-derived-chemicals-in-escherichia-coli-bl21-de3-through-iclr-and-arca-deletion
#16
Min Liu, Yamei Ding, Hailin Chen, Zhe Zhao, Huizhou Liu, Mo Xian, Guang Zhao
BACKGROUND: Acetyl-CoA-derived chemicals are suitable for multiple applications in many industries. The bio-production of these chemicals has become imperative owing to the economic and environmental problems. However, acetate overflow is the major drawback for acetyl-CoA-derived chemicals production. Approaches for overcoming acetate overflow may be beneficial for the production of acetyl-CoA-derived chemicals. RESULTS: In this study, a transcriptional regulator iclR was knocked out in E...
January 7, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28061399/transcriptome-sequencing-and-metabolic-pathways-of-astaxanthin-accumulated-in-haematococcus-pluvialis-mutant-under-15-co2
#17
Jun Cheng, Ke Li, Yanxia Zhu, Weijuan Yang, Junhu Zhou, Kefa Cen
Transcriptome sequencing and annotation was performed on Haematococcus pluvialis mutant red cells induced with high light under 15% CO2 to demonstrate why astaxanthin yield of the mutant was 1.7 times higher than that of a wild strain. It was found that 56% of 1947 differentially expressed genes were upregulated in mutant cells. Most significant differences were found in unigenes related to photosynthesis, carotenoid biosynthesis and fatty acid biosynthesis pathways. The pyruvate kinase increased by 3.5-fold in mutant cells...
December 24, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/28060484/a-highly-promiscuous-%C3%A3-ketoacyl-acp-synthase-kas-iii-like-protein-is-involved-in-pactamycin-biosynthesis
#18
Mostafa E Abugrain, Corey J Brumsted, Andrew R Osborn, Benjamin Philmus, Taifo Mahmud
β-Ketoacyl-acyl carrier protein (β-Ketoacyl-ACP) synthase (KAS) III catalyzes the first step in fatty acid biosynthesis, involving a Claisen condensation of the acetyl-CoA starter unit with the first extender unit, malonyl-ACP, to form acetoacetyl-ACP. KAS III-like proteins have also been reported to catalyze acyltransferase reactions using coenzyme A esters or discrete ACP-bound substrates. Here, we report the in vivo and in vitro characterizations of a KAS III-like protein (PtmR), which directly transfers a 6-methylsalicylyl moiety from an iterative type I polyketide synthase to an aminocyclopentitol unit in pactamycin biosynthesis...
January 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28059952/atp-citrate-lyase-genetics-molecular-biology-and-therapeutic-target-for-dyslipidemia
#19
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...
January 5, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28057705/translational-control-of-lipogenic-enzymes-in-the-cell-cycle-of-synchronous-growing-yeast-cells
#20
Heidi M Blank, Ricardo Perez, Chong He, Nairita Maitra, Richard Metz, Joshua Hill, Yuhong Lin, Charles D Johnson, Vytas A Bankaitis, Brian K Kennedy, Rodolfo Aramayo, Michael Polymenis
Translational control during cell division determines when cells start a new cell cycle, how fast they complete it, the number of successive divisions, and how cells coordinate proliferation with available nutrients. The translational efficiencies of mRNAs in cells progressing synchronously through the mitotic cell cycle, while preserving the coupling of cell division with cell growth, remain uninvestigated. We now report comprehensive ribosome profiling of a yeast cell size series from the time of cell birth, to identify mRNAs under periodic translational control...
January 5, 2017: EMBO Journal
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