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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/28209662/the-impact-of-between-analytical-platform-variability-on-the-classification-of-pleural-effusions-into-exudate-or-transudate-using-light-s-criteria
#1
Michael P Cornes, Andrew J Chadburn, Claire Thomas, Catherine Darby, Rachel Webster, Clare Ford, Rousseau Gama
BACKGROUND: Light's criteria are ratios of pleural fluid to serum total protein (TP), pleural fluid to serum lactate dehydrogenase (LDH) and pleural fluid LDH to the upper reference limit for serum LDH. They are used to classify pleural effusions into an exudate or transudate when pleural fluid protein is 25-35 g/L. We evaluated the impact of between analytical platforms on the classification of pleural effusions using Light's criteria. METHODS: Light's criteria were used to classify pleural effusions with fluid TP between 25 and 35 g/L into exudate and transudate...
February 16, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#2
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
February 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#3
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28202214/lethal-neonatal-case-and-review-of-primary-short-chain-enoyl-coa-hydratase-sceh-deficiency-associated-with-secondary-lymphocyte-pyruvate-dehydrogenase-complex-pdc-deficiency
#4
Jirair K Bedoyan, Samuel P Yang, Sacha Ferdinandusse, Rhona M Jack, Alexander Miron, George Grahame, Suzanne D DeBrosse, Charles L Hoppel, Douglas S Kerr, Ronald J A Wanders
Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and cerebrospinal fluid lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine...
February 2, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28202118/-clinical-and-laboratory-features-of-macrophage-activation-syndrome
#5
Li Guo, Mei-Ping Lu, Gui-Juan Dong, Li-Ping Teng, Yi-Ping Xu, Li-Xia Zou, Qi Zheng
OBJECTIVE: To study the clinical and laboratory features of macrophage activation syndrome (MAS) at the early stage of diagnosis, and to explore a method for early identification of MAS. METHODS: A retrospective analysis was performed for the demographic data, clinical and laboratory features, and treatment outcomes of 21 MAS patients. RESULTS: Of the 21 MAS patients, 14 had systemic juvenile idiopathic arthritis, 5 had Kawasaki disease (KD), and 2 had connective tissue disease (CTD) as primary diseases...
February 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28199108/application-of-off-rate-screening-in-the-identification-of-novel-pan-isoform-inhibitors-of-pyruvate-dehydrogenase-kinase
#6
Paul A Brough, Lisa Baker, Simon Bedford, Kirsten Brown, Seema Chavda, Victoria Chell, Jalanie D'Alessandro, Nicholas G M Davies, Ben Davis, Loic Le Strat, Alba T Macias, Daniel Maddox, Patrick C Mahon, Andrew J Massey, Natalia Matassova, Sean McKenna, Jonathan D Moore, James B Murray, Christopher J Northfield, Charles Parry, Rachel Parsons, Stephen D Roughley, Terry Shaw, Heather Simmonite, Stephen Stokes, Allan Surgenor, Emma Stefaniak, Alan Robertson, Yikang Wang, Paul Webb, Neil Whitehead, Mike Wood
Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28196956/amino-acid-catabolism-in-staphylococcus-aureus-and-the-function-of-carbon-catabolite-repression
#7
Cortney R Halsey, Shulei Lei, Jacqueline K Wax, Mckenzie K Lehman, Austin S Nuxoll, Laurey Steinke, Marat Sadykov, Robert Powers, Paul D Fey
Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM)...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196867/synaptic-activity-drives-a-genomic-program-that-promotes-a-neuronal-warburg-effect
#8
Carlos Bas-Orth, Yan-Wei Tan, David Lau, Hilmar Bading
Synaptic activity drives changes in gene expression to promote long-lasting adaptations of neuronal structure and function. One example of such an adaptive response is the buildup of acquired neuroprotection, a synaptic activity- and gene transcription-mediated increase in the resistance of neurons against harmful conditions. A hallmark of acquired neuroprotection is the stabilization of mitochondrial structure and function. We therefore re-examined previously identified sets of synaptic activity-regulated genes to identify genes that are directly linked to mitochondrial function...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28195221/transcriptome-analysis-around-the-onset-of-strawberry-fruit-ripening-uncovers-an-important-role-of-oxidative-phosphorylation-in-ripening
#9
Qing-Hua Wang, Cheng Zhao, Miao Zhang, Yu-Zhong Li, Yuan-Yue Shen, Jia-Xuan Guo
Although much progress has been made towards understanding the ripening of non-climacteric fruit using the strawberry as a model plant, the defined molecular mechanisms remain unclear. Here, RNA-sequencing was performed using four cDNA libraries around the onset of ripening, and a total of 31,793 unigenes and 335 pathways were annotated including the top five pathways, which were involved in ribosome, spliceosome, protein processing, plant-pathogen interaction and plant hormone signaling, and the important DEGs related to ripening were annotated to be mainly involved in protein translation and processing, sugar metabolism, energy metabolism, phytohormones, antioxidation, pigment and softening, especially finding a decreased trend of oxidative phosphorylation during red-coloring...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194879/ethanol-production-by-the-hyperthermophilic-archaeon-pyrococcus-furiosus-by-expression-of-bacterial-bifunctional-alcohol-dehydrogenases
#10
Matthew W Keller, Gina L Lipscomb, Diep M Nguyen, Alexander T Crowley, Gerrit J Schut, Israel Scott, Robert M Kelly, Michael W W Adams
Ethanol is an important target for the renewable production of liquid transportation fuels. It can be produced biologically from pyruvate, via pyruvate decarboxylase, or from acetyl-CoA, by alcohol dehydrogenase E (AdhE). Thermophilic bacteria utilize AdhE, which is a bifunctional enzyme that contains both acetaldehyde dehydrogenase and alcohol dehydrogenase activities. Many of these organisms also contain a separate alcohol dehydrogenase (AdhA) that generates ethanol from acetaldehyde, although the role of AdhA in ethanol production is typically not clear...
February 14, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28193910/hif1-2%C3%AE-mediates-hypoxia-induced-ldha-expression-in-human-pancreatic-cancer-cells
#11
Xin-Gang Cui, Zhi-Tao Han, Shao-Hui He, Xing-da Wu, Tian-Rui Chen, Cheng-Hao Shao, Dan-Lei Chen, Ning Su, Yuan-Ming Chen, Ting Wang, Jing Wang, Dian-Wen Song, Wang-Jun Yan, Xing-Hai Yang, Tie-Long Liu, Hai-Feng Wei, Jianru Xiao
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages...
10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192880/ameliorating-effect-of-betanin-a-natural-chromoalkaloid-by-modulating-hepatic-carbohydrate-metabolic-enzyme-activities-and-glycogen-content-in-streptozotocin-nicotinamide-induced-experimental-rats
#12
Indumathi Dhananjayan, Sujithra Kathiroli, Srinivasan Subramani, Vinothkumar Veerasamy
Betanin, a chromoalkaloid of beetroot, has shown significant biological effects of antioxidants, anti-inflammatory and anticarcinogenic activities. So, we attempted to determine whether betanin (a natural pigment) would be protective against hyperglycemia in streptozotocin (STZ) - nicotinamide (NA) induced diabetic rats. Rats were injected with STZ (40mg/kgb.w.) 15 mins after the administration of NA (110mg/kgb.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. After 72h diabetic rats were treated with betanin orally at a doses of 10, 20 and 40mg/kg b...
February 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28187683/proteomics-profiling-of-chimeric-truncated-tissue-plasminogen-activator-producing-chinese-hamster-ovary-cells-cultivated-in-a-chemically-defined-medium-supplemented-with-protein-hydrolysates
#13
Bahareh Azarian, Seyedeh Matin Sajedin, Amin Azimi, Mozhgan Raigani, Behrouz Vaziri, Fatemeh Davami
Background: Culture media enrichment through the addition of protein hydrolysates is beneficial for achieving higher protein expression. Methods: In this study, designing the optimum mixture of four soy and casein-derived hydrolysates was successfully performed by design of experiment and specific productivity increased in all predicted combinations. Protein profile of recombinant CHO (rCHO) cells producing tissue plasminogen activator in a serum-free medium (SFM) supplemented with designed hydrolysate additives was compared to that of rCHO cells cultivated in SFM...
11, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28183841/mathematical-modeling-links-wnt-signaling-to-emergent-patterns-of-metabolism-in-colon-cancer
#14
Mary Lee, George T Chen, Eric Puttock, Kehui Wang, Robert A Edwards, Marian L Waterman, John Lowengrub
Cell-intrinsic metabolic reprogramming is a hallmark of cancer that provides anabolic support to cell proliferation. How reprogramming influences tumor heterogeneity or drug sensitivities is not well understood. Here, we report a self-organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted array. To understand this pattern, we developed a reaction-diffusion model that incorporates Wnt signaling, a pathway known to upregulate PDK1 and Warburg metabolism...
February 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#15
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28179188/diacetyl-and-related-flavorant-%C3%AE-diketones-biotransformation-cellular-interactions-and-respiratory-tract-toxicity
#16
M W Anders
Exposure to diacetyl and related α-diketones causes respiratory-tract damage in humans and experimental animals. Chemical toxicity is often associated with covalent modification of cellular nucleophiles by electrophilic chemicals. Electrophilic α-diketones may covalently modify nucleophilic arginine residues in critical proteins and, thereby, produce the observed respiratory-tract pathology. The major pathway for the biotransformation of α-diketones is reduction to α-hydroxyketones (acyloins), which is catalyzed by NAD(P)H-dependent enzymes of the short-chain dehydrogenase/reductase (SDR) and the aldo-keto reductase (AKR) superfamilies...
February 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28178567/defective-branched-chain-amino-acid-catabolism-disrupts-glucose-metabolism-and-sensitizes-the-heart-to-ischemia-reperfusion-injury
#17
Tao Li, Zhen Zhang, Stephen C Kolwicz, Lauren Abell, Nathan D Roe, Maengjo Kim, Bo Zhou, Yang Cao, Julia Ritterhoff, Haiwei Gu, Daniel Raftery, Haipeng Sun, Rong Tian
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28174304/the-pyruvate-and-%C3%AE-ketoglutarate-dehydrogenase-complexes-of-pseudomonas-aeruginosa-catalyze-pyocyanin-and-phenazine-1-carboxylic-acid-reduction-via-the-subunit-dihydrolipoamide-dehydrogenase
#18
Nathaniel R Glasser, Benjamin X Wang, Julie A Hoy, Dianne K Newman
Phenazines are a class of redox-active molecules produced by diverse bacteria and archaea. Many of the biological functions of phenazines, such as mediating signaling, iron acquisition, and redox homeostasis, derive from their redox activity. While prior studies have focused on extracellular phenazine oxidation by oxygen and iron, here we report a search for reductants and catalysts of intracellular phenazine reduction in Pseudomonas aeruginosa Enzymatic assays in cell-free lysate, together with crude fractionation and chemical inhibition, indicate that P...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28163135/a-mechanism-based-pharmacokinetic-enzyme-turnover-model-for-dichloroacetic-acid-auto-inhibition-in-rats
#19
Yu Jiang, Gary Milavetz, Margaret O James, Guohua An
Dichloroacetic acid (DCA), a halogenated organic acid, is a pyruvate dehydrogenase kinase (PDK) inhibitor that has been used to treat congenital or acquired lactic acidosis and is currently in early phase clinical trials for cancer treatment. DCA was found to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta 1 (GSTZ1-1), resulting in non-linear kinetics and abnormally high accumulation ratio after repeated dosing. In this analysis, a semi-mechanistic pharmacokinetic-enzyme turn over model was developed for the first time to capture DCA auto-inhibition, gastrointestinal region-dependent absorption, and time dependent change in bioavailability in rats...
February 2, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28159812/right-ventricular-metabolism-during-veno-arterial-extracorporeal-membrane-oxygenation-in-immature-swine-heart-in-vivo
#20
Masaki Kajimoto, Dolena R Ledee, Nancy G Isern, Michael A Portman
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and therefore enhances functional recovery. The RV must often assume systemic ventricular pressures and function upon weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown...
February 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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