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NADH AND NAD+

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https://www.readbyqxmd.com/read/29349500/exogenous-h2s-switches-cardiac-energy-substrate-metabolism-by-regulating-sirt3-expression-in-db-db-mice
#1
Yu Sun, Zhiliang Tian, Ning Liu, Linxue Zhang, Zhaopeng Gao, Xiaojiao Sun, Miao Yu, Jichao Wu, Fan Yang, Yajun Zhao, Huan Ren, He Chen, Dechao Zhao, Yan Wang, Shiyun Dong, Changqing Xu, Fanghao Lu, Weihua Zhang
Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD + -dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice...
January 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29341594/designing-flavoprotein-gfp-fusion-probes-for-analyte-specific-ratiometric-fluorescence-imaging
#2
Devin A Hudson, Jeffrey L Caplan, Colin Thorpe
The development of genetically encoded fluorescent probes for analyte-specific imaging has revolutionized our understanding of intracellular processes. Current classes of intracellular probes depend on the selection of binding domains that either undergo conformational changes on analyte binding or can be linked to thiol redox chemistry. Here we have designed novel probes by fusing a flavoenzyme, whose fluorescence is quenched on reduction by the analyte of interest, with a GFP domain to allow for rapid and specific ratiometric sensing...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29337692/generation-of-superoxide-and-hydrogen-peroxide-by-side-reactions-of-mitochondrial-2-oxoacid-dehydrogenase-complexes-in-isolation-and-in-cells
#3
Victoria I Bunik, Martin D Brand
Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate, branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen. Studies using isolated mitochondria in media mimicking cytosol suggest that the 2-oxoacid dehydrogenase complexes contribute little to the production of superoxide or hydrogen peroxide relative to other mitochondrial sites at physiological steady-states...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#4
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29327656/nad-nadh-homeostasis-affects-metabolic-adaptation-to-hypoxia-and-secondary-metabolite-production-in-filamentous-fungi
#5
Motoyuki Shimizu
Filamentous fungi are used to produce fermented foods, organic acids, beneficial secondary metabolites and various enzymes. During such processes, these fungi balance cellular NAD+:NADH ratios to adapt to environmental redox stimuli. Cellular NAD(H) status in fungal cells is a trigger of changes in metabolic pathways including those of glycolysis, fermentation, and the production of organic acids, amino acids and secondary metabolites. Under hypoxic conditions, high NADH:NAD+ ratios lead to the inactivation of various dehydrogenases, and the metabolic flow involving NAD+ is down-regulated compared with normoxic conditions...
January 12, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29297957/enhanced-1-3-propanediol-production-in-klebsiella-pneumoniae-by-a-combined-strategy-of-strengthening-the-tca-cycle-and-weakening-the-glucose-effect
#6
Xinyao Lu, Shunli Ren, Jingzheng Lu, Hong Zong, Jian Song, Bin Zhuge
AIMS: This study aimed to strengthen the reducing equivalent regeneration in Klebsiella pneumoniae for improving 1,3-propanediol (PDO) production. METHODS AND RESULTS: Disruption of the arcA gene activated the transcription levels of the TCA cycle genes and thus increased the NADH/NAD+ ratio by 54.2%, leading to the improved PDO titer and yield per cell from 16.1 g l-1 and 4.0 g gDCW-1 to 18.8 g l-1 and 6.4 g gDCW-1 , respectively. Further ldhA gene deletion eliminated lactate accumulation and promoted the PDO titer to 19...
January 3, 2018: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29297253/oligomeric-forms-of-bacterial-malate-dehydrogenase-a-study-of-the-enzyme-from-the-phototrophic-non-sulfur-bacterium-rhodovulum-steppense-a-20s
#7
Alexander T Eprintsev, Marina I Falaleeva, Maya S Lyashchenko, Ilya Y Toropygin, Abir U Igamberdiev
Malate dehydrogenase (EC 1.1.1.37) was purified to homogeneity from the phototrophic purple non-sulfur bacterium Rhodovulum steppense A-20s. According to gel-chromatography and electrophoretic studies, malate dehydrogenase is present as a dimer, tetramer and octamer depending on cultivation conditions. In phototrophic aerobic conditions only the tetrameric form was present, in chemotrophic aerobic conditions all three forms were detected, while in the absence of oxygen the octameric form disappeared. The malate dehydrogenase oligomers are encoded by a single gene and composed of the same 35 kDa polypeptide but differ in pH and temperature optimum, in affinities to malate, oxaloacetate, NADH and NAD+ and in regulation by cations and citrate...
January 3, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29288336/cytotoxicity-of-propofol-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#8
Koji Kido, Hiroyuki Ito, Yudai Yamamoto, Koshi Makita, Tokujiro Uchida
PURPOSE: Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10)...
December 29, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/29285300/renal-oncocytoma-characterized-by-the-defective-complex-i-of-the-respiratory-chain-boosts-the-synthesis-of-the-ros-scavenger-glutathione
#9
Gerrit Kürschner, Qingzhou Zhang, Rosanna Clima, Yi Xiao, Jonas Felix Busch, Ergin Kilic, Klaus Jung, Nikolaus Berndt, Sascha Bulik, Hermann-Georg Holzhütter, Giuseppe Gasparre, Marcella Attimonelli, Mohan Babu, David Meierhofer
Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29261292/haloacetic-acid-water-disinfection-by-products-affect-pyruvate-dehydrogenase-activity-and-disrupt-cellular-metabolism
#10
Azra Dad, Clara Hyunhee Jeong, Elizabeth D Wagner, Michael J Plewa
The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown...
December 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29245965/the-aldehyde-group-of-gossypol-induces-mitochondrial-apoptosis-via-ros-sirt1-p53-puma-pathway-in-male-germline-stem-cell
#11
Xin He, Chongyang Wu, Yanhua Cui, Haijing Zhu, Zhiming Gao, Bo Li, Jinlian Hua, Baoyu Zhao
As a widely grown economic crop, cotton is the major oil and protein resource for human and livestock. But the highly toxic of gossypol in cottonseed severely restricts its effective utilization, consequently creating huge resource waste. Previous studies have shown the male germline stem cells were the most vulnerable cells in gossypol damages, but the mechanism was still unclear. We found gossypol induced cell viability decline resulted from apoptosis. And the increase of Caspase-9 activity in gossypol treatment hinted the mitochondrial apoptosis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29242353/cardiac-specific-bdh1-overexpression-ameliorates-oxidative-stress-and-cardiac-remodeling-in-pressure-overload-induced-heart-failure
#12
Motoki Uchihashi, Atsushi Hoshino, Yoshifumi Okawa, Makoto Ariyoshi, Satoshi Kaimoto, Shuhei Tateishi, Kazunori Ono, Ryoetsu Yamanaka, Daichi Hato, Yohei Fushimura, Sakiko Honda, Kuniyoshi Fukai, Yusuke Higuchi, Takehiro Ogata, Eri Iwai-Kanai, Satoaki Matoba
BACKGROUND: Energy starvation and the shift of energy substrate from fatty acids to glucose is the hallmark of metabolic remodeling during heart failure progression. However, ketone body metabolism in the failing heart has not been fully investigated. METHODS AND RESULTS: Microarray data analysis and mitochondrial isobaric tags for relative and absolute quantification proteomics revealed that the expression of D-β-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the NAD+/NADH coupled interconversion of acetoacetate and β-hydroxybutyrate, was increased 2...
December 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29239720/akt-regulation-of-glycolysis-mediates-bioenergetic-stability-in-epithelial-cells
#13
Yin P Hung, Carolyn Teragawa, Nont Kosaisawe, Taryn E Gillies, Michael Pargett, Marta Minguet, Kevin Distor, Briana L Rocha-Gregg, Jonathan L Coloff, Mark A Keibler, Gregory Stephanopoulos, Gary Yellen, Joan S Brugge, John G Albeck
Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using fluorescent reporters for AMPK activity, Akt activity, and cytosolic NADH/NAD+ redox. Across various conditions, including glycolytic or mitochondrial inhibition or cell proliferation, we observed distinct patterns of AMPK activity, including both stable adaptation and highly dynamic behaviors such as periodic oscillations and irregular fluctuations that indicate a failure to reach a steady state...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29236080/three-dimensional-analysis-of-the-interactions-between-hldh5-and-its-inhibitors
#14
REVIEW
Giulio Poli, Carlotta Granchi, Mohamed Aissaoui, Filippo Minutolo, Tiziano Tuccinardi
Inhibitors of human lactate dehydrogenase (hLDH5)-the enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD⁺-are promising therapeutic agents against cancer because this enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. Consequently, significant efforts have been made for the identification of small-molecule hLDH5 inhibitors displaying high inhibitory potencies. X-ray structure of hLDH5 complexes as well as molecular modeling studies contribute to identify and explain the main binding modes of hLDH5 inhibitors reported in literature...
December 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29228460/emissive-synthetic-cofactors-enzymatic-interconversions-of-tza-analogues-of-atp-nad-nadh-nadp-and-nadph
#15
Yitzhak Tor, François Hallé, Andrea Fin, Alexander R Rovira
A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3-d]pyrimidine analogue of adenosine (tzA), is described. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tzATP to yield NtzAD+, which can be enzymatically phosphorylated by NAD+ kinase and ATP or tzATP to the corresponding NtzADP+. The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to NtzADPH by glucose-6-phosphate dehydrogenase and reoxidation to NtzADP+ by glutathione reductase...
December 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29226071/structural-enzymology-comparisons-of-multifunctional-enzyme-type-1-mfe1-the-flexibility-of-its-dehydrogenase-part
#16
Prasad Kasaragod, Getnet B Midekessa, Shruthi Sridhar, Werner Schmitz, Tiila-Riikka Kiema, Jukka K Hiltunen, Rik K Wierenga
Multifunctional enzyme, type-1 (MFE1) is a monomeric enzyme with a 2E-enoyl-CoA hydratase and a 3S-hydroxyacyl-CoA dehydrogenase (HAD) active site. Enzyme kinetic data of rat peroxisomal MFE1 show that the catalytic efficiencies for converting the short-chain substrate 2E-butenoyl-CoA into acetoacetyl-CoA are much lower when compared with those of the homologous monofunctional enzymes. The mode of binding of acetoacetyl-CoA (to the hydratase active site) and the very similar mode of binding of NAD + and NADH (to the HAD part) are described and compared with those of their monofunctional counterparts...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29225823/human-mitochondrial-mthfd2-is-a-dual-redox-cofactor-specific-methylenetetrahydrofolate-dehydrogenase-methenyltetrahydrofolate-cyclohydrolase
#17
Minhye Shin, Jessica Momb, Dean R Appling
Background: Folate-dependent one-carbon metabolism provides one-carbon units for several biological processes. This pathway is highly compartmentalized in eukaryotes, with the mitochondrial pathway producing formate for use in cytoplasmic processes. The mitochondrial enzyme MTHFD2 has been reported to use NAD+ as a cofactor while the isozyme MTHFD2L utilizes NAD+ or NADP+ at physiologically relevant conditions. Because MTHFD2 is highly expressed in many cancer types, we sought to determine the cofactor preference of this enzyme...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/29224355/structural-features-and-domain-movements-controlling-substrate-binding-and-cofactor-specificity-in-class-ii-hmg-coa-reductase
#18
Bradley R Miller, Yan Kung
The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although HMGR inhibition by statin drugs is well understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range in cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data on the enzyme's cofactor preferences...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29214999/engineering-an-aldehyde-dehydrogenase-toward-its-substrates-3-hydroxypropanal-and-nad-for-enhancing-the-production-of-3-hydroxypropionic-acid
#19
Ye Seop Park, Un Jong Choi, Nguyen Hoai Nam, Sang Jin Choi, Abdul Nasir, Sun-Gu Lee, Kyung Jin Kim, Gyoo Yeol Jung, Sangdun Choi, Jeung Yeop Shim, Sunghoon Park, Tae Hyeon Yoo
3-Hydroxypropionic acid (3-HP) can be produced via the biological route involving two enzymatic reactions: dehydration of glycerol to 3-hydroxypropanal (3-HPA) and then oxidation to 3-HP. However, commercial production of 3-HP using recombinant microorganisms has been hampered with several problems, some of which are associated with the toxicity of 3-HPA and the efficiency of NAD+ regeneration. We engineered α-ketoglutaric semialdehyde dehydrogenase (KGSADH) from Azospirillum brasilense for the second reaction to address these issues...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29213318/targeted-redox-and-energy-cofactor-metabolomics-in-clostridium-thermocellum-and-thermoanaerobacterium-saccharolyticum
#20
Kyle Sander, Keiji G Asano, Deepak Bhandari, Gary J Van Berkel, Steven D Brown, Brian Davison, Timothy J Tschaplinski
Background: Clostridium thermocellum and Thermoanaerobacterium saccharolyticum are prominent candidate biocatalysts that, together, can enable the direct biotic conversion of lignocellulosic biomass to ethanol. The imbalance and suboptimal turnover rates of redox cofactors are currently hindering engineering efforts to achieve higher bioproductivity in both organisms. Measuring relevant intracellular cofactor concentrations will help understand redox state of these cofactors and help identify a strategy to overcome these limitations; however, metabolomic determinations of these labile metabolites have historically proved challenging...
2017: Biotechnology for Biofuels
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