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succinyl CoA-ligase

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https://www.readbyqxmd.com/read/29625225/metabolic-engineering-of-escherichia-coli-for-producing-adipic-acid-through-the-reverse-adipate-degradation-pathway
#1
Mei Zhao, Dixuan Huang, Xiaojuan Zhang, Mattheos A G Koffas, Jingwen Zhou, Yu Deng
Adipic acid is an important dicarboxylic acid mainly used for the production of nylon 6-6 fibers and resins. Previous studies focused on the biological production of adipic acid directly from different substrates, resulting in low yields and titers. In this study, a five-step reverse adipate-degradation pathway (RADP) identified in Thermobifida fusca has been reconstructed in Escherichia coli BL21 (DE3). The resulting strain (Mad136) produced 0.3gL-1 adipic acid with a 11.1% theoretical yield in shaken flasks, and we confirmed that the step catalyzed by 5-carboxy-2-pentenoyl-CoA reductase (Tfu_1647) as the rate-limiting step of the RADP...
April 3, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29458925/is-cupping-blister-harmful-a-proteomical-analysis-of-blister-fluid-induced-by-cupping-therapy-and-scald
#2
Zhidan Liu, Chunlan Chen, Xiaoyan Li, Chuang Zhao, Zunyuan Li, Wei Liang, Yufang Lin
OBJECTIVE: Cupping therapy has a long history in traditional medicine especially in Asian countries. It was controversial whether cupping induced blisters are beneficial to healing effects, and the formation and content in the blisters remain unexplored. We aimed to identify and compare the molecular components of the blister fluid from the cupping therapy and the scalds to explore the necessary of inducing cupping induced blisters. METHODS: Fluid sample of blisters from fifteen patients receiving cupping therapy (Cupping group) and scald burns (Scald group) were collected in this study...
February 2018: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29217198/clinical-molecular-and-computational-analysis-in-two-cases-with-mitochondrial-encephalomyopathy-associated-with-suclg1-mutation-in-a-consanguineous-family
#3
Marwa Maalej, Amel Tej, Jihène Bouguila, Samia Tilouche, Senda Majdoub, Boudour Khabou, Mouna Tabbebi, Rahma Felhi, Marwa Ammar, Emna Mkaouar-Rebai, Leila Keskes, Lamia Boughamoura, Faiza Fakhfakh
Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28803913/synthetic-rescue-couples-nadph-generation-to-metabolite-overproduction-in-saccharomyces-cerevisiae
#4
Siavash Partow, Patrick B Hyland, Radhakrishnan Mahadevan
Engineering the redox cofactor metabolism is known to be a key challenge in developing a platform strain for biosynthesis of valuable products. Hence, general strategies for manipulation of co-factor metabolism in industrially relevant hosts are of significance. Here, we demonstrate an improvement in α-ketoglutarate (AKG) production in S. cerevisiae using a novel approach based on synthetic rescue. Here, we first perturb the cytosolic NADPH metabolism via deletion of glucose-6-phosphate dehydrogenase (ZWF1)...
August 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28709933/identification-of-novel-biomarker-and-therapeutic-target-candidates-for-diagnosis-and-treatment-of-follicular-carcinoma
#5
Xianyin Lai, Christopher B Umbricht, Kurt Fisher, Justin Bishop, Qiuying Shi, Shaoxiong Chen
Distinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Identification of biomarkers for improving diagnostic accuracy is important for clinical management. Meanwhile, it is critical to identify therapeutic target candidates for treatment of follicular carcinoma. Currently, no reliable diagnostic protein biomarkers and therapeutic targets are available. To explore novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to analyze control, follicular adenoma, and follicular carcinoma using formalin-fixed, paraffin-embedded tissue samples...
August 23, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28495375/methylene-blue-stimulates-substrate-level-phosphorylation-catalysed-by-succinyl-coa-ligase-in-the-citric-acid-cycle
#6
T Komlódi, L Tretter
Methylene blue (MB), a potential neuroprotective agent, is efficient in various neurodegenerative disease models. Beneficial effects of MB have been attributed to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP) results in the production of ATP independent from the ATP synthase (ATP-ase). In energetically compromised mitochondria, ATP produced by SLP can prevent the reversal of the adenine nucleotide translocase and thus the hydrolysis of glycolytic ATP. The aim of the present study was to investigate the effect of MB on mitochondrial SLP catalysed by succinyl-CoA ligase...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28267914/activity-based-protein-profiling-leads-to-identification-of-novel-protein-targets-for-nerve-agent-vx
#7
Dan Carmany, Andrew J Walz, Fu-Lian Hsu, Bernard Benton, David Burnett, Jennifer Gibbons, Daan Noort, Trevor Glaros, Jennifer W Sekowski
Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects...
April 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28161514/biosorption-behavior-and-proteomic-analysis-of-escherichia-coli-p4-under-cadmium-stress
#8
Zaman Khan, Abdul Rehman, Muhammad Atif Nisar, Saima Zafar, Inga Zerr
Bacteria develop a variety of adaptations at transcriptomic, metabolomic and proteomic levels in order to survive potentially damaging environmental perturbations. Present study is exploring the fluctuations in proteome of E. coli P4 to knob Cd(+2)-induced cytotoxicity. An attempt was also made to integrate all these approaches to gain comprehensive insight of Cd(+2) stress response in E. coli P4. This study is exposing the altered behavior of various proteins and their underlying metabolic pathways which have previously not been reported with reference to Cd(+2) stress such as sulfoquinovose biosynthesis and degradation pathway...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28017724/deficiency-of-succinyl-coa-synthetase-%C3%AE-subunit-delays-development-impairs-locomotor-activity-and-reduces-survival-under-starvation-in-drosophila
#9
Xiuming Quan, Yukiko Sato-Miyata, Manabu Tsuda, Keigo Muramatsu, Tsunaki Asano, Satomi Takeo, Toshiro Aigaki
Succinyl-CoA synthetase/ligase (SCS) is a mitochondrial enzyme that catalyzes the reversible process from succinyl-CoA to succinate and free coenzyme A in TCA cycle. SCS deficiencies are implicated in mitochondrial hepatoencephalomyopathy in humans. To investigate the impact of SCS deficiencies in Drosophila, we generated a null mutation in Scs alpha subunit (Scsα) using the CRISPR/Cas9 system, and characterized their phenotype. We found that the Drosophila SCS deficiency, designated ScsαKO , contained a high level of succinyl-CoA, a substrate for the enzyme, and altered levels of various metabolites in TCA cycle and glycolysis, indicating that the energy metabolism was impaired...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913098/succinyl-coa-synthetase-sucla2-deficiency-in-two-siblings-with-impaired-activity-of-other-mitochondrial-oxidative-enzymes-in-skeletal-muscle-without-mitochondrial-dna-depletion
#10
Xiaoping Huang, Jirair K Bedoyan, Didem Demirbas, David J Harris, Alexander Miron, Simone Edelheit, George Grahame, Suzanne D DeBrosse, Lee-Jun Wong, Charles L Hoppel, Douglas S Kerr, Irina Anselm, Gerard T Berry
Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype...
March 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27688912/comparative-proteomic-analysis-of-differential-proteins-in-response-to-aqueous-extract-of-quercus-infectoria-gall-in-methicillin-resistant-staphylococcus-aureus
#11
Radhiah Khairon, Noraziah Mohamad Zin, Mariati Abdul Rahman, Dayang Fredalina Basri
The aim of this study is to analyze the differential proteins in MRSA ATCC 33591 treated with aqueous extract from Q. infectoria gall. Protein extracts were obtained from MRSA cells by sonication and were separated by 2D polyacrylamide gels. Protein spots of interest were extracted from the gels and identified using LC-ESI-QTOF MS. The concentration of Q. infectoria extract used for 2D-gel electrophoresis was subinhibitory concentration. Minimum inhibitory concentration (MIC) value of the extract against MRSA was 19...
2016: International Journal of Proteomics
https://www.readbyqxmd.com/read/27551855/differential-gel-electrophoresis-dige-evaluation-of-naphthoimidazoles-mode-of-action-a-study-in-trypanosoma-cruzi-bloodstream-trypomastigotes
#12
Giselle Villa Flor Brunoro, Vitor Marcel Faça, Marcelle Almeida Caminha, André Teixeira da Silva Ferreira, Monique Trugilho, Kelly Cristina Gallan de Moura, Jonas Perales, Richard Hemmi Valente, Rubem Figueiredo Sadok Menna-Barreto
BACKGROUND: The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active...
August 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27484306/expanding-the-phenotypic-spectrum-of-succinyl-coa-ligase-deficiency-through-functional-validation-of-a-new-suclg1-variant
#13
Taraka R Donti, Ruchi Masand, Daryl A Scott, William J Craigen, Brett H Graham
Deficiency of the TCA cycle enzyme Succinyl-CoA Synthetase/Ligase (SCS), due to pathogenic variants in subunits encoded by SUCLG1 and SUCLA2, causes mitochondrial encephalomyopathy, methylmalonic acidemia, and mitochondrial DNA (mtDNA) depletion. In this study, we report an 11year old patient who presented with truncal ataxia, chorea, hypotonia, bilateral sensorineural hearing loss and preserved cognition. Whole exome sequencing identified a heterozygous known pathogenic variant and a heterozygous novel missense variant of uncertain clinical significance (VUS) in SUCLG1...
September 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27143079/-clinical-and-laboratory-studies-on-four-chinese-patients-with-succinate-coa-ligase-deficiency-noticed-by-mild-methylmalonic-aciduria
#14
Y P Liu, X Y Li, Y Ding, Q Wang, J Q Song, Y Zhang, D X Li, Y P Qin, Y L Yang
OBJECTIVE: To study the clinical and genetic features of the patients with secondary methylmalonic aciduria due to succinate-CoA ligase deficiency. METHOD: From February 2011 to April 2014, 4 Chinese patients with succinate-CoA ligase deficiency and mild methylmalonic aciduria were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and mutations were analyzed. RESULT: Four patients presented with severe psychomotor retardation, hypotonia, seizures, feeding problems and failure to thrive from the age of one day to 6 months...
May 2016: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/27052834/a-krebs-cycle-component-limits-caspase-activation-rate-through-mitochondrial-surface-restriction-of-crl-activation
#15
Lior Aram, Tslil Braun, Carmel Braverman, Yosef Kaplan, Liat Ravid, Smadar Levin-Zaidman, Eli Arama
How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids...
April 4, 2016: Developmental Cell
https://www.readbyqxmd.com/read/26952923/novel-mutation-in-sucla2-identified-on-sequencing-analysis
#16
Olcay Güngör, Ahmet Kağan Özkaya, Gülay Güngör, Kadri Karaer, Cengiz Dilber, Kürşad Aydin
Succinate-CoA ligase, ADP-forming, beta subunit (SUCLA2)-related mitochondrial DNA depletion syndrome is caused by mutations affecting the ADP-using isoform of the beta subunit in succinyl-CoA synthase, which is involved in the Krebs cycle. The SUCLA2 protein is found mostly in heart, skeletal muscle, and brain tissues. SUCLA2 mutations result in a mitochondrial disorder that manifests as deafness, lesions in the basal ganglia, and encephalomyopathy accompanied by dystonia. Such mutations are generally associated with mildly increased plasma methylmalonic acid, increased plasma lactate, elevated plasma carnitine esters, and the presence of methylmalonic acid in urine...
July 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/26867592/proteomics-analysis-of-high-lipid-producing-strain-mucor-circinelloides-wj11-an-explanation-for-the-mechanism-of-lipid-accumulation-at-the-proteomic-level
#17
Xin Tang, Xinyi Zan, Lina Zhao, Haiqin Chen, Yong Q Chen, Wei Chen, Yuanda Song, Colin Ratledge
BACKGROUND: The oleaginous fungus, Mucor circinelloides, is attracting considerable interest as it produces oil rich in γ-linolenic acid. Nitrogen (N) deficiency is a common strategy to trigger the lipid accumulation in oleaginous microorganisms. Although a simple pathway from N depletion in the medium to lipid accumulation has been elucidated at the enzymatic level, global changes at protein levels upon N depletion have not been investigated. In this study, we have systematically analyzed the changes at the levels of protein expression in M...
2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/26610654/novel-remodeling-of-the-mouse-heart-mitochondrial-proteome-in-response-to-acute-insulin-stimulation
#18
B A Pedersen, P G Yazdi, J F Taylor, O S Khattab, Y-H Chen, Y Chen, P H Wang
BACKGROUND AND AIM: Mitochondrial dysfunction contributes to the pathophysiology of diabetic cardiomyopathy. The aim of this study was to investigate the acute changes in the mitochondrial proteome in response to insulin stimulation. METHODS AND RESULTS: Cardiac mitochondria from C57BL/6 mice after insulin stimulation were analyzed using two-dimensional fluorescence difference gel electrophoresis. MALDI-TOF MS/MS was utilized to identify differences. Two enzymes involved in metabolism and four structural proteins were identified...
December 2015: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/26358042/abolition-of-mitochondrial-substrate-level-phosphorylation-by-itaconic-acid-produced-by-lps-induced-irg1-expression-in-cells-of-murine-macrophage-lineage
#19
Beáta Németh, Judit Doczi, Dániel Csete, Gergely Kacso, Dora Ravasz, Daniel Adams, Gergely Kiss, Adam M Nagy, Gergo Horvath, Laszlo Tretter, Attila Mócsai, Roland Csépányi-Kömi, Iordan Iordanov, Vera Adam-Vizi, Christos Chinopoulos
Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as a product of an enzyme encoded by immunoresponsive gene 1 (Irg1), acting on the citric acid cycle intermediate cis-aconitate. In mitochondria, itaconate can be converted by succinate-coenzyme A (CoA) ligase to itaconyl-CoA at the expense of ATP (or GTP), and is also a weak competitive inhibitor of complex II. Here, we investigated specific bioenergetic effects of increased itaconate production mediated by LPS-induced stimulation of Irg1 in murine bone marrow-derived macrophages (BMDM) and RAW-264...
January 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/26027540/genomic-and-clinicopathologic-features-of-primary-myelofibrosis-with-isolated-13q-deletion
#20
Meenakshi Mehrotra, Keyur P Patel, Tianjian Chen, Roberto N Miranda, Yaping Wang, Zhuang Zuo, Ramya Muddasani, Bal M Mishra, Ronald Abraham, Rajyalakshmi Luthra, Gary Lu
BACKGROUND: Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features in PMF are poorly understood. Characterization of genomic alternations in PMF helps to determine their association with clinicopathologic features for further therapeutic implications. PATIENTS AND METHODS: In this retrospective study, we investigated genomic changes using array-based comparative genomic hybridization (aCGH) in 17 PMF patients with isolated del(13q) and confirmed our aCGH findings with quantitative polymerase chain reaction (PCR) assay...
August 2015: Clinical Lymphoma, Myeloma & Leukemia
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