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NADH AND NAD+

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https://www.readbyqxmd.com/read/28327357/the-ternary-complex-structure-of-d-mandelate-dehydrogenase-with-nadh-and-anilino-oxo-acetate
#1
Nayuta Furukawa, Akimasa Miyanaga, Masahiro Nakajima, Hayao Taguchi
Enterococcus faecium NAD-dependent d-mandelate dehydrogenase (D-ManDH) belongs to a ketopantoate reductase (KPR)-related D-2-hydroxyacid dehydrogenase family, and exhibits broad substrate specificity toward bulky hydrophobic 2-ketoacids, preferring C3-branched substrates. The ternary complex structure of D-ManDH with NADH and anilino(oxo)acetate (AOA) revealed that the substrate binding induces a shear motion of the N-terminal domain along the C-terminal domain, following the hinge motion induced by the NADH binding, and allows the bound NADH molecule to form favorable interactions with a 2-ketoacid substrate...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28318242/whole-blood-metabolomics-by-1h-nmr-spectroscopy-provides-a-new-opportunity-to-evaluate-coenzymes-and-antioxidants
#2
G A Nagana Gowda, Daniel Raftery
Conventional human blood metabolomics employs serum or plasma and provides a wealth of metabolic information therein. However, this approach lacks the ability to measure and evaluate important metabolites such as coenzymes that are present at high concentrations in red blood cells. As an important alternative to serum/plasma metabolomics, we show here that a simple 1H NMR experiment can simultaneously measure coenzymes and antioxidants in extracts of whole human blood, in addition to the nearly 70 metabolites that were shown to be quantitated in serum/plasma, recently [Anal...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anemia-cells-to-glycolytic-metabolism
#3
Enrico Cappelli, Paola Cuccarolo, Giorgia Stroppiana, Maurizio Miano, Roberta Bottega, Vanessa Cossu, Paolo Degan, Silvia Ravera
Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28303934/redox-sensing-regulator-rex-regulates-aerobic-metabolism-morphological-differentiation-and-avermectin-production-in-streptomyces-avermitilis
#4
Xingchao Liu, Yaqing Cheng, Mengya Lyu, Ying Wen, Yuan Song, Zhi Chen, Jilun Li
The regulatory role of redox-sensing regulator Rex was investigated in Streptomyces avermitilis. Eleven genes/operons were demonstrated to be directly regulated by Rex; these genes/operons are involved in aerobic metabolism, morphological differentiation, and secondary metabolism. Rex represses transcription of target genes/operons by binding to Rex operator (ROP) sequences in the promoter regions. NADH reduces DNA-binding activity of Rex to target promoters, while NAD(+) competitively binds to Rex and modulates its DNA-binding activity...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303408/methylene-blue-decreases-mitochondrial-lysine-acetylation-in-the-diabetic-heart
#5
Jessica M Berthiaume, Chia-Heng Hsiung, Alison B Austin, Sean P McBrayer, Mikayla M Depuydt, Margaret P Chandler, Masaru Miyagi, Mariana G Rosca
Diabetic cardiomyopathy is preceded by mitochondrial alterations, and progresses to heart failure. We studied whether treatment with methylene blue (MB), a compound that was reported to serve as an alternate electron carrier within the mitochondrial electron transport chain (ETC), improves mitochondrial metabolism and cardiac function in type 1 diabetes. MB was administered at 10 mg/kg/day to control and diabetic rats. Both echocardiography and hemodynamic studies were performed to assess cardiac function...
March 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28287662/base-assisted-c-c-coupling-between-carbonyl-and-polypyridyl-ligands-in-a-ru-nadh-type-carbonyl-complex
#6
Debashis Ghosh, Takashi Fukushima, Katsuaki Kobayashi, Susan Sen, Susumu Kitagawa, Tatsuhisa Kato, Koji Tanaka
A reaction of a ruthenium(ii) NAD-type complex, [Ru(tpy)(pbn)(Cl)](+) (tpy = 2,2':6',2''-terpyridine; pbn = 2-(pyridin-2-yl)benzo[b][1,5]naphthyridine), with pressurized CO (2 MPa) at 150 °C in H2O selectively produced a two-electron reduced ruthenium(ii)-NADH-type carbonyl complex, [Ru(tpy)(pbnHH)(CO)](2+) (pbnHH = 2-(pyridin-2-yl)-5,10-dihydrobenzo[b][1,5]naphthyridine), rather than the oxidized [Ru(tpy)(pbn)(CO)](2+) complex. Indeed, [Ru(tpy)(pbnHH)(CO)](2+) was quantitatively oxidized to [Ru(tpy)(pbn)(CO)](2+) upon treatment with one equiv...
March 13, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28286806/assessment-of-cellular-redox-state-using-nad-p-h-fluorescence-intensity-and-lifetime
#7
Thomas S Blacker, Tunde Berecz, Michael R Duchen, Gyorgy Szabadkai
NADH and NADPH are redox cofactors, primarily involved in catabolic and anabolic metabolic processes respectively. In addition, NADPH plays an important role in cellular antioxidant defence. In live cells and tissues, the intensity of their spectrally-identical autofluorescence, termed NAD(P)H, can be used to probe the mitochondrial redox state, while their distinct enzyme-binding characteristics can be used to separate their relative contributions to the total NAD(P)H intensity using fluorescence lifetime imaging microscopy (FLIM)...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28279944/adipose-tissue-nad-homeostasis-sirtuins-and-poly-adp-ribose-polymerases-important-players-in-mitochondrial-metabolism-and-metabolic-health
#8
REVIEW
Riikka Jokinen, Sini Pirnes-Karhu, Kirsi H Pietiläinen, Eija Pirinen
Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions...
February 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28265794/characterization-of-frex-as-an-nadh-sensor-for-in-vivo-applications-in-the-presence-of-nad-and-at-various-ph-values
#9
Svea Wilkening, Franz-Josef Schmitt, Marius Horch, Ingo Zebger, Oliver Lenz, Thomas Friedrich
The fluorescent biosensor Frex, recently introduced as a sensitive tool to quantify the NADH concentration in living cells, was characterized by time-integrated and time-resolved fluorescence spectroscopy regarding its applicability for in vivo measurements. Based on the purified sensor protein, it is shown that the NADH dependence of Frex fluorescence can be described by a Hill function with a concentration of half-maximal sensor response of K D  ≈ 4 µM and a Hill coefficient of n ≈ 2. Increasing concentrations of NADH have moderate effects on the fluorescence lifetime of Frex, which changes by a factor of two from about 500 ps in the absence of NADH to 1 ns under fluorescence-saturating NADH concentrations...
March 6, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28261868/in-vivo-assessment-of-intracellular-redox-state-in-rat-liver-using-hyperpolarized-1-13-c-alanine
#10
Jae Mo Park, Chalermchai Khemtong, Shie-Chau Liu, Ralph E Hurd, Daniel M Spielman
PURPOSE: The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD(+) ]. In this study, we assessed the use of hyperpolarized [1-(13) C]alanine and the subsequent detection of the intracellular products of [1-(13) C]pyruvate and [1-(13) C]lactate as a useful substrate for assessing redox levels in the liver in vivo. METHODS: Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion...
March 5, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28261181/clustered-genes-encoding-2-keto-l-gulonate-reductase-and-l-idonate-5-dehydrogenase-in-the-novel-fungal-d-glucuronic-acid-pathway
#11
Joosu Kuivanen, Mikko Arvas, Peter Richard
D-Glucuronic acid is a biomass component that occurs in plant cell wall polysaccharides and is catabolized by saprotrophic microorganisms including fungi. A pathway for D-glucuronic acid catabolism in fungal microorganisms is only partly known. In the filamentous fungus Aspergillus niger, the enzymes that are known to be part of the pathway are the NADPH requiring D-glucuronic acid reductase forming L-gulonate and the NADH requiring 2-keto-L-gulonate reductase that forms L-idonate. With the aid of RNA sequencing we identified two more enzymes of the pathway...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28258794/brain-bioenergetics-and-redox-state-measured-by-31-p-magnetic-resonance-spectroscopy-in-unaffected-siblings-of-patients-with-psychotic-disorders
#12
Virginie-Anne Chouinard, Sang-Young Kim, Linda Valeri, Cagri Yuksel, Kyle P Ryan, Guy Chouinard, Bruce M Cohen, Fei Du, Dost Öngür
BACKGROUND: Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using (31)P-magnetic resonance spectroscopy ((31)P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls. METHODS: 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent (31)P-MRS in the frontal lobe (6×6×4cm(3)) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression...
March 1, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28258322/metabolic-engineering-of-synechocystis-sp-pcc-6803-for-enhanced-ethanol-production-based-on-flux-balance-analysis
#13
Katsunori Yoshikawa, Yoshihiro Toya, Hiroshi Shimizu
Synechocystis sp. PCC 6803 is an attractive host for bio-ethanol production due to its ability to directly convert atmospheric carbon dioxide into ethanol using photosystems. To enhance ethanol production in Synechocystis sp. PCC 6803, metabolic engineering was performed based on in silico simulations, using the genome-scale metabolic model. Comprehensive reaction knockout simulations by flux balance analysis predicted that the knockout of NAD(P)H dehydrogenase enhanced ethanol production under photoautotrophic conditions, where ammonium is the nitrogen source...
March 3, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28246386/mycoplasma-bovis-nadh-oxidase-functions-as-both-a-nadh-oxidizing-and-o2-reducing-enzyme-and-an-adhesin
#14
Gang Zhao, Hui Zhang, Xi Chen, Xifang Zhu, Yusi Guo, Chenfei He, Farhan Anwar Khan, Yingyu Chen, Changmin Hu, Huanchun Chen, Aizhen Guo
Mycoplasma bovis causes considerable economic losses in the cattle industry worldwide. In mycoplasmal infections, adhesion to the host cell is of the utmost importance. In this study, the amino acid sequence of NOX was predicted to have enzymatic domains. The nox gene was then cloned and expressed in Escherichia coli. The enzymatic activity of recombinant NOX (rNOX) was confirmed based on its capacity to oxidize NADH to NAD(+) and reduce O2 to H2O2. The adherence of rNOX to embryonic bovine lung (EBL) cells was confirmed with confocal laser scanning microscopy, enzyme-linked immunosorbent assay, and flow cytometry...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28243985/efficient-synthesis-of-s-n-boc-3-hydroxypiperidine-using-an-r-specific-carbonyl-reductase-from-candida-parapsilosis
#15
Jingjing Chen, Ming Yan, Lin Xu
(S)-N-Boc-3-hydroxypiperidine (S-NBHP) is a critical chiral intermediate in the synthesis of pharmaceuticals, including ibrutinib, the active pharmaceutical ingredient of the new drug Imbruvica approved for the treatment of lymphoma. An (R)-specific carbonyl reductase from Candida parapsilosis (CprCR, also known as R-specific alcohol dehydrogenase) that catalyzes asymmetric reduction to produce (S)-N-Boc-3-hydroxypiperidine (S-NBHP) was identified for the first time. When co-expressed with a glucose dehydrogenase from Bacillus megaterium in Escherichia coli Rosetta (DE3), recombinant crude enzyme exhibited an activity of 9 U/mg with N-Boc-3-piperidone as the substrate and 12 U/mg with glucose as the substrate...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28243982/construction-of-pyruvate-producing-strain-with-intact-pyruvate-dehydrogenase-and-genome-wide-transcription-analysis
#16
Maohua Yang, Xiang Zhang
To obtain strain YP211 with a high tendency for accumulating pyruvate, central metabolic pathways were modified in Escherichia coli MG1655. Specifically, seven genes (ldhA, pflB, pta-ackA, poxB, ppc, frdBC) were knocked out sequentially and full pyruvate dehydrogenase was retained. In batch fermentation with M9 medium, pyruvate yield and production rate reached 0.63 g/g glucose and 1.89 g/(1 h), respectively. Meanwhile, the production of acetate, succinate, and other carboxylates was effectively controlled...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28242228/protein-s-glutathionylation-alters-superoxide-hydrogen-peroxide-emission-from-pyruvate-dehydrogenase-complex
#17
Marisa O'Brien, Julia Chalker, Liam Slade, Danielle Gardiner, Ryan J Mailloux
Pyruvate dehydrogenase (Pdh) is a vital source of reactive oxygen species (ROS) in several different tissues. Pdh has also been suggested to serve as a mitochondrial redox sensor. Here, we report that O2(•-)/ H2O2 emission from pyruvate dehydrogenase (Pdh) is altered by S-glutathionylation. Glutathione disulfide (GSSG) amplified O2(•-)/ H2O2 production by purified Pdh during reverse electron transfer (RET) from NADH. Thiol oxidoreductase glutaredoxin-2 (Grx2) reversed these effects confirming that Pdh is a target for S-glutathionylation...
February 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28230641/peritransplant-energy-changes-and-their-correlation-to-outcome-after-human-liver-transplantation
#18
Bote G Bruinsma, James H Avruch, Gautham V Sridharan, Pepijn D Weeder, Marie Louise Jacobs, Kerry Crisalli, Beth Amundsen, Robert J Porte, James F Markmann, Korkut Uygun, Heidi Yeh
BACKGROUND: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. METHODS: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD, NADPH/NADP, FAD, GSSG/GSH)...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28223550/nadh-autofluorescence-a-new-metabolic-biomarker-for-cancer-stem-cells-identification-of-vitamin-c-and-cape-as-natural-products-targeting-stemness
#19
Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B Tanowitz, Michael P Lisanti
Here, we assembled a broad molecular "tool-kit" to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to "metabolic fractionation" by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for "stem cell activity", using the mammosphere assay (3D-spheroids)...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202712/ribeye-b-domain-binds-to-lipid-components-of-synaptic-vesicles-in-an-nad-h-dependent-redox-sensitive-manner
#20
Karin Schwarz, Frank Schmitz
Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and is necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain, which binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicle (SV)s. How this physical contact between ribbons and synaptic vesicles is established at a molecular level is not well understood...
March 20, 2017: Biochemical Journal
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