scholarly journals Postharvest Drying Techniques Regulate Secondary Metabolites and Anti-Neuroinflammatory Activities of Ganoderma lucidum

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4484
Author(s):  
Nooruddin-bin Sadiq ◽  
Da-Hye Ryu ◽  
Jwa-Yeong Cho ◽  
A-Hyeon Lee ◽  
Dae-Geun Song ◽  
...  
Keyword(s):  
Map Kinase ◽  
Ganoderma Lucidum ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Fructose Bisphosphate ◽  
Primary Metabolite ◽  
Ganoderic Acids ◽  
Bv2 Cells ◽  
Freeze Dried ◽  
Bv2 Microglia

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at −80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity

2011 ◽  
Vol 111 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Lorenzo K. Love ◽  
Paul J. LeBlanc ◽  
J. Greig Inglis ◽  
Nicolette S. Bradley ◽  
Jon Choptiany ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Endurance Training ◽  
Aerobic Capacity ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Carbohydrate Oxidation ◽  
Pyruvate Dehydrogenase Phosphatase

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity ( r2 = 0.399, P = 0.001) and PDP1 protein expression ( r2 = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α ( r2 = 0.310, P = 0.002) and PDK2 protein ( r2 = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼18% of the variance in PDP activity ( r2 = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼38% of the variance in PDP activity ( r2 = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).

Saccharomyces cerevisiae contains two functional citrate synthase genes

1986 ◽  
Vol 6 (6) ◽  
pp. 1936-1942
Author(s):  
K S Kim ◽  
M S Rosenkrantz ◽  
L Guarente
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Nuclear Gene ◽  
Tricarboxylic Acid ◽  
Yeast Genome ◽  
Gene Encoding ◽  
Acid Cycle ◽  
Nonfermentable Carbon Source

The tricarboxylic acid cycle occurs within the mitochondria of the yeast Saccharomyces cerevisiae. A nuclear gene encoding the tricarboxylic acid cycle enzyme citrate synthase has previously been isolated (M. Suissa, K. Suda, and G. Schatz, EMBO J. 3:1773-1781, 1984) and is referred to here as CIT1. We report here the isolation, by an immunological method, of a second nuclear gene encoding citrate synthase (CIT2). Disruption of both genes in the yeast genome was necessary to produce classical citrate synthase-deficient phenotypes: glutamate auxotrophy and poor growth on rich medium containing lactate, a nonfermentable carbon source. Therefore, the citrate synthase produced from either gene was sufficient for these metabolic roles. Transcription of both genes was maximally repressed in medium containing both glucose and glutamate. However, transcription of CIT1 but not of CIT2 was derepressed in medium containing a nonfermentable carbon source. The significance of the presence of two genes encoding citrate synthase in S. cerevisiae is discussed.

scholarly journals Bacterial cell cycle control by citrate synthase independent of enzymatic activity

2019 ◽  
Author(s):  
Matthieu Bergé ◽  
Julian Pezzatti ◽  
Víctor González-Ruiz ◽  
Laurence Degeorges ◽  
Serge Rudaz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Citrate Synthase ◽  
Caulobacter Crescentus ◽  
Tricarboxylic Acid Cycle ◽  
Cell Cycle Control ◽  
Tca Cycle ◽  
Cell Cycle Regulators ◽  
Central Metabolism ◽  
Cycle Enzyme

ABSTRACTCoordination of cell cycle progression with central metabolism is fundamental to all cell types and likely underlies differentiation into dispersal cells in bacteria. How central metabolism is monitored to regulate cell cycle functions is poorly understood. A forward genetic selection for cell cycle regulators in the polarized alpha-proteobacterium Caulobacter crescentus unearthed the uncharacterized CitA citrate synthase, a TCA (tricarboxylic acid) cycle enzyme, as unprecedented checkpoint regulator of the G1→S transition. We show that loss of the CitA protein provokes a (p)ppGpp alarmone-dependent G1-phase arrest without apparent metabolic or energy insufficiency. While S-phase entry is still conferred when CitA is rendered catalytically inactive, the paralogous CitB citrate synthase has no overt role other than sustaining TCA cycle activity when CitA is absent. With eukaryotic citrate synthase paralogs known to fulfill regulatory functions, our work extends the moonlighting paradigm to citrate synthase coordinating central (TCA) metabolism with development and perhaps antibiotic tolerance in bacteria.

scholarly journals Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

2021 ◽  
Author(s):  
Joy Omini ◽  
Izabela Wojciechowska ◽  
Aleksandra Skirycz ◽  
Hideaki Moriyama ◽  
Toshihiro Obata
Keyword(s):  
Malate Dehydrogenase ◽  
Metabolic Flux ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Feedback Regulation ◽  
Dynamic Structure ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Enzyme Complex ◽  
Acetyl Coa

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle 'metabolon' which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was presented together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.

scholarly journals Tricarboxylic acid cycle and proton gradient in Pandoravirus massiliensis: Is it still a virus?

2020 ◽  
Author(s):  
Sarah Aherfi ◽  
Djamal Brahim Belhaouari ◽  
Lucile Pinault ◽  
Jean-Pierre Baudoin ◽  
Philippe Decloquement ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Isocitrate Dehydrogenase ◽  
Energy Production ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Proton Gradient ◽  
Giant Virus ◽  
Acid Cycle ◽  
Key Enzyme

ABSTRACTSince the discovery of Acanthamoeba polyphaga Mimivirus, the first giant virus of amoeba, the historical hallmarks defining a virus have been challenged. Giant virion sizes can reach up to 2.3 µm, making them visible by optical microscopy. They have large genomes of up to 2.5 Mb that encode proteins involved in the translation apparatus. Herein, we investigated possible energy production in Pandoravirus massiliensis, the largest of our giant virus collection. MitoTracker and TMRM mitochondrial membrane markers allowed for the detection of a membrane potential in virions that could be abolished by the use of the depolarizing agent CCCP. An attempt to identify enzymes involved in energy metabolism revealed that 8 predicted proteins of P. massiliensis exhibited low sequence identities with defined proteins involved in the universal tricarboxylic acid cycle (acetyl Co-A synthase; citrate synthase; aconitase; isocitrate dehydrogenase; α-ketoglutarate decarboxylase; succinate dehydrogenase; fumarase). All 8 viral predicted ORFs were transcribed together during viral replication, mainly at the end of the replication cycle. Two of these proteins were detected in mature viral particles by proteomics. The product of the ORF132, a predicted protein of P. massiliensis, cloned and expressed in Escherichia coli, provided a functional isocitrate dehydrogenase, a key enzyme of the tricarboxylic acid cycle, which converts isocitrate to α-ketoglutarate. We observed that membrane potential was enhanced by low concentrations of Acetyl-CoA, a regulator of the tricarboxylic acid cycle. Our findings show for the first time that energy production can occur in viruses, namely, pandoraviruses, and the involved enzymes are related to tricarboxylic acid cycle enzymes. The presence of a proton gradient in P. massiliensis coupled with the observation of genes of the tricarboxylic acid cycle make this virus a form a life for which it is legitimate to question ‘what is a virus?’.

scholarly journals Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4359
Author(s):  
Qi Zhang ◽  
Jing Zhou ◽  
Mi Shen ◽  
Hui Xu ◽  
Shu Yu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Pyrroloquinoline Quinone ◽  
Transmission Electron ◽  
Bv2 Cells ◽  
Mitochondrial Functions ◽  
Tnf Α ◽  
Bv2 Microglia ◽  
Factor Α

Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson’s disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

Tricarboxylic acid cycle dehydrogenases inhibition by naringenin: experimental and molecular modelling evidence

2020 ◽  
Vol 123 (10) ◽  
pp. 1117-1126
Author(s):  
Pauline Maciel August ◽  
Mateus Grings ◽  
Marcelo Sartori Grunwald ◽  
Geancarlo Zanatta ◽  
Vinícius Stone ◽  
...  
Keyword(s):  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Tricarboxylic Acid ◽  
Metabolic Effects ◽  
Similar Reduction ◽  
Acid Cycle ◽  
Docking Simulations ◽  
Female Wistar Rats

AbstractThe study of polyphenols’ effects on health has been gaining attention lately. In addition to reacting with important enzymes, altering the cell metabolism, these substances can present either positive or negative metabolic alterations depending on their consumption levels. Naringenin, a citrus flavonoid, already presents diverse metabolic effects. The objective of this work was to evaluate the effect of maternal naringenin supplementation during pregnancy on the tricarboxylic acid cycle activity in offspring’s cerebellum. Adult female Wistar rats were divided into two groups: (1) vehicle (1 ml/kg by oral administration (p.o.)) or (2) naringenin (50 mg/kg p.o.). The offspring were euthanised at 7th day of life, and the cerebellum was dissected to analyse citrate synthase, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH) and malate dehydrogenase (MDH) activities. Molecular docking used SwissDock web server and FORECASTER Suite, and the proposed binding pose image was created on UCSF Chimera. Data were analysed by Student’s t test. Naringenin supplementation during pregnancy significantly inhibited IDH, α-KGDH and MDH activities in offspring’s cerebellum. A similar reduction was observed in vitro, using purified α-KGDH and MDH, subjected to pre-incubation with naringenin. Docking simulations demonstrated that naringenin possibly interacts with dehydrogenases in the substrate and cofactor binding sites, inhibiting their function. Naringenin administration during pregnancy may affect cerebellar development and must be evaluated with caution by pregnant women and their physicians.

scholarly journals Improved ganoderic acids production in Ganoderma lucidum by wood decaying components

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yanru Hu ◽  
Shakeel Ahmed ◽  
Jiawei Li ◽  
Biaobiao Luo ◽  
Zengyan Gao ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Ganoderic Acids

Carbohydrate metabolism in Acanthamoeba castellanii. 1. The activity of key enzymes and [14C]-glucose metabolism

1973 ◽  
Vol 19 (9) ◽  
pp. 1131-1136 ◽  
Author(s):  
Lansing M. Prescott ◽  
Harold E. Hoyme ◽  
Darlene Crockett ◽  
Elena Hui
Keyword(s):  
Carbohydrate Metabolism ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Fumarate Hydratase ◽  
Acanthamoeba Castellanii ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Glyceraldehydephosphate Dehydrogenase

The specific activities of a number of the key enzymes involved in carbohydrate metabolism in Acanthamoeba castellanii (Neff clone I–12) have been determined. The following Embden–Meyerhof and pentose phosphate pathway enzymes were present: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, hexokinase, phosphofructokinase, hexose diphosphatase, aldolase, glyceraldehydephosphate dehydrogenase, pyruvate kinase, and pyruvate-phosphate dikinase. The following tricarboxylic acid cycle enzymes were also found: citrate synthase, aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and malate dehydrogenase. The degradation of glucose-U-14C to 14CO2 was examined. Aerobic 14CO2 production from glucose-U-14C was 3.4-fold greater than anaerobic production. The data provide further evidence that the Embden–Meyerhof, pentose phosphate, and tricarboxylic acid cycle pathways are probably functional in A. castellanii.

scholarly journals Enhancement of Ganoderic Acid Accumulation by Overexpression of an N-Terminally Truncated 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene in the Basidiomycete Ganoderma lucidum

2012 ◽  
Vol 78 (22) ◽  
pp. 7968-7976 ◽  
Author(s):  
Jun-Wei Xu ◽  
Yi-Ning Xu ◽  
Jian-Jiang Zhong
Keyword(s):  
Ganoderma Lucidum ◽  
Coenzyme A ◽  
Catalytic Domain ◽  
Selection Marker ◽  
Transformation System ◽  
Protein Subunit ◽  
Ganoderic Acid ◽  
Content Type ◽  
Ganoderic Acids ◽  
Coenzyme A Reductase

ABSTRACTGanoderic acids produced byGanoderma lucidum, a well-known traditional Chinese medicinal mushroom, exhibit antitumor and antimetastasis activities. Genetic modification ofG. lucidumis difficult but critical for the enhancement of cellular accumulation of ganoderic acids. In this study, a homologous genetic transformation system forG. lucidumwas developed for the first time using mutatedsdhB, encoding the iron-sulfur protein subunit of succinate dehydrogenase, as a selection marker. The truncatedG. lucidumgene encoding the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) was overexpressed by using theAgrobacterium tumefaciens-mediated transformation system. The results showed that the mutatedsdhBsuccessfully conferred carboxin resistance upon transformation. Most of the integrated transfer DNA (T-DNA) appeared as a single copy in the genome. Moreover, deregulated constitutive overexpression of the HMGR gene led to a 2-fold increase in ganoderic acid content. It also increased the accumulation of intermediates (squalene and lanosterol) and the upregulation of downstream genes such as those of farnesyl pyrophosphate synthase, squalene synthase, and lanosterol synthase. This study demonstrates that transgenic basidiomyceteG. lucidumis a promising system to achieve metabolic engineering of the ganoderic acid pathway.

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