The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Martha H Stipanuk - One of the best experts on this subject based on the ideXlab platform.
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the Cysteine dioxgenase knockout mouse altered Cysteine Metabolism in nonhepatic tissues leads to excess h2s hs production and evidence of pancreatic and lung toxicity
Antioxidants & Redox Signaling, 2013Co-Authors: Heather B Roman, Lawrence L Hirschberger, Jakub Krijt, Alessandro Valli, Viktor Kožich, Martha H StipanukAbstract:Abstract Aims: To define the consequences of loss of Cysteine dioxygenase (CDO) on Cysteine Metabolism at the tissue level, we determined levels of relevant metabolites and enzymes and evidence of H2S/HS− (gaseous hydrogen sulfide and its conjugate base) toxicity in liver, pancreas, kidney, and lung of CDO−/− mice that were fed either a taurine-free or taurine-supplemented diet. Results: CDO−/− mice had low tissue and serum taurine and hypotaurine levels and high tissue levels of Cysteine, consistent with the loss of CDO. CDO−/− mice had elevated urinary excretion of thiosulfate, high tissue and serum cystathionine and lanthionine levels, and evidence of inhibition and destabilization of cytochrome c oxidase, which is consistent with excess production of H2S/HS−. Accumulation of cystathionine and lanthionine appeared to result from cystathionine β-synthase (CBS)-mediated Cysteine desulfhydration. Very high levels of hypotaurine in pancreas of wild-type mice and very high levels of cystathionine and lanthi...
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The Cysteine dioxgenase knockout mouse: altered Cysteine Metabolism in nonhepatic tissues leads to excess H2S/HS(-) production and evidence of pancreatic and lung toxicity.
Antioxidants & Redox Signaling, 2013Co-Authors: Heather B Roman, Lawrence L Hirschberger, Jakub Krijt, Alessandro Valli, Viktor Kožich, Martha H StipanukAbstract:Abstract Aims: To define the consequences of loss of Cysteine dioxygenase (CDO) on Cysteine Metabolism at the tissue level, we determined levels of relevant metabolites and enzymes and evidence of H2S/HS− (gaseous hydrogen sulfide and its conjugate base) toxicity in liver, pancreas, kidney, and lung of CDO−/− mice that were fed either a taurine-free or taurine-supplemented diet. Results: CDO−/− mice had low tissue and serum taurine and hypotaurine levels and high tissue levels of Cysteine, consistent with the loss of CDO. CDO−/− mice had elevated urinary excretion of thiosulfate, high tissue and serum cystathionine and lanthionine levels, and evidence of inhibition and destabilization of cytochrome c oxidase, which is consistent with excess production of H2S/HS−. Accumulation of cystathionine and lanthionine appeared to result from cystathionine β-synthase (CBS)-mediated Cysteine desulfhydration. Very high levels of hypotaurine in pancreas of wild-type mice and very high levels of cystathionine and lanthi...
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Dealing with methionine/homoCysteine sulfur: Cysteine Metabolism to taurine and inorganic sulfur
Journal of Inherited Metabolic Disease, 2011Co-Authors: Martha H Stipanuk, Iori UekiAbstract:Synthesis of Cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homoCysteine degradation, with Cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homoCysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H_2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the Cysteine thiol by Cysteine dioxygenase to form Cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative Metabolism of Cysteine by desulfuration versus oxidative pathways is influenced by Cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when Cysteine is deficient, whereas oxidative catabolism dominates when Cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of Cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to Cysteine availability and may function to provide a pathway to siphon Cysteine to less toxic metabolites than those produced by Cysteine desulfuration reactions.
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dealing with methionine homoCysteine sulfur Cysteine Metabolism to taurine and inorganic sulfur
Journal of Inherited Metabolic Disease, 2011Co-Authors: Martha H Stipanuk, Iori UekiAbstract:Synthesis of Cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homoCysteine degradation, with Cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homoCysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the Cysteine thiol by Cysteine dioxygenase to form Cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative Metabolism of Cysteine by desulfuration versus oxidative pathways is influenced by Cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when Cysteine is deficient, whereas oxidative catabolism dominates when Cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of Cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to Cysteine availability and may function to provide a pathway to siphon Cysteine to less toxic metabolites than those produced by Cysteine desulfuration reactions.
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mammalian Cysteine Metabolism new insights into regulation of Cysteine Metabolism
Journal of Nutrition, 2006Co-Authors: Martha H Stipanuk, John E Dominy, Relicardo M ColosoAbstract:The mammalian liver tightly regulates its free Cysteine pool, and intracellular Cysteine in rat liver is maintained between 20 and 100 nmol/g even when sulfur amino acid intakes are deficient or excessive. By keeping Cysteine levels within a narrow range and by regulating the synthesis of glutathione, which serves as a reservoir of Cysteine, the liver addresses both the need to have adequate Cysteine to support normal Metabolism and the need to keep Cysteine levels below the threshold of toxicity. Cysteine catabolism is tightly regulated via regulation of Cysteine dioxygenase (CDO) levels in the liver, with the turnover of CDO protein being dramatically decreased when intracellular Cysteine levels increase. This occurs in response to changes in the intracellular Cysteine concentration via changes in the rate of CDO ubiquitination and degradation. Glutathione synthesis also increases when intracellular Cysteine levels increase as a result of increased saturation of glutamate-Cysteine ligase (GCL) with Cysteine, and this contributes to removal of excess Cysteine. When Cysteine levels drop, GCL activity increases, and the increased capacity for glutathione synthesis facilitates conservation of Cysteine in the form of glutathione (although the absolute rate of glutathione synthesis still decreases because of the lack of substrate). This increase in GCL activity is dependent on up-regulation of expression of both the catalytic and modifier subunits of GCL, resulting in an increase in total catalytic subunit plus an increase in the catalytic efficiency of the enzyme. An important role of Cysteine utilization for coenzyme A synthesis in maintaining cellular Cysteine levels in some tissues, and a possible connection between the necessity of controlling cellular Cysteine levels to regulate the rate of hydrogen sulfide production, have been suggested by recent literature and are areas that deserve further study.
Yong Zhang - One of the best experts on this subject based on the ideXlab platform.
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real time visualization of Cysteine Metabolism in living cells with ratiometric fluorescence probes
Analytical Chemistry, 2018Co-Authors: Bingying Xu, Haibo Zhou, Wei Tang, Cuilan Zhang, Shengsong Deng, Yong ZhangAbstract:Sulfite from Cysteine Metabolism in living cells plays a crucial role in improving the water solubility of metabolic xenobiotics for their easier excretion in urine or bile. However, an imbalance of sulfite in vivo would lead to oxidative stress or age-related diseases, and an effective strategy for real-time imaging of Cysteine Metabolism in living cells is still lacking due to its low metabolite concentration and rapid reaction kinetics. Herein, a cyanine moiety based ratiometric fluorescence probe was developed for highly selective and sensitive detection of sulfite in aqueous solution and living cells. The free probe exhibited an orange emission color, and the fluorescence color would gradually change to blue once sulfite anions selectively reacted with the unsaturated carbon double bonds in the probe molecule. This ratiometric fluorescence manner endowed the probe excellent sensitivity with a detection limit of 0.78 nM, which was then explored to image the kinetic process of sulfite release in hepati...
Isabelle Martinverstraete - One of the best experts on this subject based on the ideXlab platform.
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plcra a new quorum sensing regulator from bacillus cereus plays a role in oxidative stress responses and Cysteine Metabolism in stationary phase
PLOS ONE, 2012Co-Authors: Eugenie Huillet, Isabelle Martinverstraete, Marcel H Tempelaars, Gwenaelle Andreleroux, Pagakrong Wanapaisan, Ludovic Bridoux, Samira Makhzami, Watanalai PanbangredAbstract:We characterized a new quorum-sensing regulator, PlcRa, which is present in various members of the B. cereus group and identified a signaling heptapeptide for PlcRa activity: PapRa7. We demonstrated that PlcRa is a 3D structural paralog of PlcR using sequence analysis and homology modeling. A comparison of the transcriptomes at the onset of stationary phase of a ΔplcRa mutant and the wild-type B. cereus ATCC 14579 strain showed that 68 genes were upregulated and 49 genes were downregulated in the ΔplcRa mutant strain (>3-fold change). Genes involved in the Cysteine Metabolism (putative CymR regulon) were downregulated in the ΔplcRa mutant strain. We focused on the gene with the largest difference in expression level between the two conditions, which encoded -AbrB2- a new regulator of the AbrB family. We demonstrated that purified PlcRa bound specifically to the abrB2 promoter in the presence of synthetic PapRa7, in an electrophoretic mobility shift assay. We further showed that the AbrB2 regulator controlled the expression of the yrrT operon involved in methionine to Cysteine conversion. We found that the ΔplcRa mutant strain was more sensitive to hydrogen peroxide- and disulfide-induced stresses than the wild type. When cystine was added to the culture of the ΔplcRa mutant, challenged with hydrogen peroxide, growth inhibition was abolished. In conclusion, we identified a new RNPP transcriptional regulator in B. cereus that activated the oxidative stress response and Cysteine Metabolism in transition state cells.
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cymr the master regulator of Cysteine Metabolism in staphylococcus aureus controls host sulphur source utilization and plays a role in biofilm formation
Molecular Microbiology, 2009Co-Authors: Olga Soutourina, Antoine Danchin, Olivier Poupel, Jeanyves Coppee, Tarek Msadek, Isabelle MartinverstraeteAbstract:Summary We have characterized the master regulator of Cysteine Metabolism, CymR, in Staphylococcus aureus. CymR repressed the transcription of genes involved in pathways leading to Cysteine formation. Eight direct DNA targets were identified using gel-shift or footprinting experiments. Comparative transcriptome analysis and in vitro studies indicated that CysM, the OAS-thiol-lyase, was also implicated in this regulatory system. OAS, the direct precursor of Cysteine, prevents CymR-dependent binding to DNA. This study has allowed us to predict sulphur Metabolism functions for previously uncharacterized S. aureus genes. We show that S. aureus is able to grow on homoCysteine as the sole sulphur source suggesting efficient MccA and MccB-dependent conversion of this compound into Cysteine. We propose that SA1850 is a new thiosulphate transporter and that TcyP and TcyABC are l-cystine transporters. CymR directly controls the use of sulphur sources of human origin such as taurine and homoCysteine. The cymR mutant also displayed a reduced capacity to form biofilms, indicating that CymR is involved in controlling this process in S. aureus via an ica-independent mechanism. These data indicate that fine-tuning of sulphur Metabolism plays an important part in the physiology of this major pathogen and its adaptation to environmental conditions and survival in the host.
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the cymr regulator in complex with the enzyme cysk controls Cysteine Metabolism in bacillus subtilis
Journal of Biological Chemistry, 2008Co-Authors: Catherine Tanous, Marie-françoise Hullo, Olga Soutourina, Antoine Danchin, Bertrand Raynal, Peggy Mervelet, Annemarie Gilles, Philippe Noirot, Patrick England, Isabelle MartinverstraeteAbstract:Abstract Several enzymes have evolved as sensors in signal transduction pathways to control gene expression, thereby allowing bacteria to adapt efficiently to environmental changes. We recently identified the master regulator of Cysteine Metabolism in Bacillus subtilis, CymR, which belongs to the poorly characterized Rrf2 family of regulators. We now report that the signal transduction mechanism controlling CymR activity in response to Cysteine availability involves the formation of a stable complex with CysK, a key enzyme for Cysteine biosynthesis. We carried out a comprehensive quantitative characterization of this regulator-enzyme interaction by surface plasmon resonance and analytical ultracentrifugation. We also showed that O-acetylserine plays a dual role as a substrate of CysK and as an effector modulating the CymR-CysK complex formation. The ability of B. subtilis CysK to bind to CymR appears to be correlated to the loss of its capacity to form a Cysteine synthase complex with CysE. We propose an original model, supported by the determination of the intracellular concentrations of the different partners, by which CysK positively regulates CymR in sensing the bacterial Cysteine pool.
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global control of Cysteine Metabolism by cymr in bacillus subtilis
Journal of Bacteriology, 2006Co-Authors: Sergine Even, Olga Soutourina, Pierre Burguiere, Sandrine Auger, Antoine Danchin, Isabelle MartinverstraeteAbstract:Sulfur is a crucial atom in Cysteine and methionine, as well as in several coenzymes and cofactors such as thiamine, biotin, or coenzyme A (CoA). Among these compounds, Cysteine is important for the biogenesis of [Fe-S] clusters, for the catalytic sites of several enzymes, and for protein folding and assembly via the formation of disulfide bonds. Moreover, Cysteine-derived proteins such as thioredoxin play a central role in protection against oxidative stress. Two major Cysteine biosynthetic pathways have been described: the thiolation pathway requiring sulfide and the reverse transsulfuration pathway, which converts homoCysteine to Cysteine with the intermediary formation of cystathionine (49). In Bacillus subtilis, the pathway of Cysteine synthesis from sulfate has been characterized (Fig. (Fig.1).1). Sulfate is first transported into the cell via a sulfate permease, CysP, related to inorganic phosphate transporters (26). Sulfate is subsequently reduced to sulfide, probably in four steps involving the sequential action of ATP sulfurylase, adenosine 5′-phosphosulfate (APS) kinase, 3′-phosphoadenosine 5′-phosphosulfate (PAPS) reductase, and sulfite reductase (3, 27, 55). An O-acetylserine thiol-lyase, the cysK gene product, further condenses sulfide and O-acetylserine (OAS) to form Cysteine (55). Several aliphatic sulfonates can be used as alternative sulfur sources for the synthesis of Cysteine. They are taken up by a sulfonate ATP-binding cassette (ABC) transporter and then converted into sulfite by an FMNH2-dependent monooxygenase (56) (Fig. (Fig.1).1). Bacillus subtilis can also use methionine as the sole sulfur source, indicating efficient conversion of methionine into Cysteine. The YrhA and YrhB proteins are involved in this conversion (S. Auger and M. F. Hullo, unpublished results). The transport of l-cystine has also been recently investigated. Three systems are present in B. subtilis: two ABC transporters, TcyABC and TcyJKLMN; and a symporter, TcyP (4). The TcyJKLMN and TcyP uptake systems are high-affinity transporters with apparent Km values for l-cystine of 2.5 μM and 0.6 μM, respectively. In addition, the TcyJKLMN system is involved in the uptake of cystathionine, S-methyl-Cysteine, djenkolic acid, and other sulfur compounds (4, 47). The tcyJKLMN genes belong to a large operon (operon ytmI), which also encodes a riboflavin kinase, two putative flavin-dependent monooxygenases, a putative acetyltransferase, and a putative amidohydrolase (6, 47, 50, 51). The expression of the ytmI operon and the tcyP gene is regulated in response to sulfur availability, while the expression level of the tcyABC operon remains low under all conditions tested (4). Moreover, expression of the ytmI operon is induced by disulfide and oxidative stresses or in a strain depleted of thioredoxin A (23, 31, 48) and repressed by the Spx protein in sulfate-containing media (7). ytmI expression is controlled in response to sulfur availability by two different regulators, YtlI and YrzC (5, 6, 51). The YtlI regulator activates the transcription of the ytmI operon by direct binding to its promoter region. Expression of the ytlI gene itself is controlled by the negative regulator YrzC. A potential cis-acting target site for the YrzC protein has been identified just upstream from the −35 box of the ytlI promoter (5). However, direct binding of YrzC to the ytlI promoter region remains to be demonstrated. Interestingly, the cascade of regulation of ytmI-type operons involving YtlI and YrzC-like regulators seems to be conserved in Listeria species (5). YrzC shares similarities with regulators of the Rrf2 family, which includes IscR, the repressor of the iscRSUA operon of Escherichia coli involved in [Fe-S] cluster biogenesis. IscR when associated with a [2Fe-2S] cluster appears to repress iscRSUA expression (44). In Desulfovibrio vulgaris, inactivation of the rrf2 gene results in overexpression of the hmc operon, which encodes a redox protein involved in electron transport during hydrogen oxidation with sulfate as an electron acceptor (18). RirA of Rhizobium leguminosarum is crucial for the genetic response to iron availability (58). NsrR of Nitromonas europaea is a nitrite-sensitive repressor of the nirK gene encoding a nitrite reductase (2). FIG. 1. Biosynthesis and recycling pathways of sulfur-containing amino acids. The enzymes present in B. subtilis are indicated by the corresponding genes: cysP, sulfate permease; sat, ATP sulfurylase; cysC, APS kinase; cysH, APS-PAPS reductase; ssuBACD, aliphatic ... In B. subtilis, several mechanisms of regulation are involved in the control of methionine and Cysteine Metabolism. The S-box transcription antitermination system controls the expression of genes participating in methionine uptake, biosynthesis, and recycling, in response to methionine availability (1, 16, 29, 46). In addition, two LysR-type regulators, CysL and YtlI, play a role in the regulation of sulfur Metabolism. CysL positively controls expression of the cysJI operon encoding the sulfite reductase by binding to its promoter region (11). YtlI is a positive regulator of the ytmI operon, as discussed above (6). However, the key regulator controlling Cysteine Metabolism in this bacterium remains to be characterized. YrzC, which indirectly regulates the synthesis of the TcyJKLMN l-cystine ABC transporter, could play this role. To determine whether YrzC is a global regulator, the expression profiles of a wild-type B. subtilis strain and a ΔyrzC mutant grown with sulfate as the sole sulfur source were compared. Using this approach, we found that expression of several genes participating in Cysteine Metabolism was derepressed in a ΔyrzC mutant. Moreover, YrzC-dependent binding to the promoter region of seven genes or operons was observed. A cis-acting DNA motif required for this binding was characterized.
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Cysteine Metabolism and its regulation in bacteria
2006Co-Authors: Eric Guedon, Isabelle MartinverstraeteAbstract:Sulfur is necessary for the synthesis of Cysteine. Microorganisms can use sulfate, thiosulfate or sulfonates as sole sulfur sources. These compounds are taken up by specific transporters followed by the conversion of sulfate or sulfonates into sulfide in 2 to 4 steps. The biosynthesis of Cysteine from serine in bacteria is carried out by a two-step pathway beginning with the O-acetylation of serine, followed by O-re placement of the acetyl group by sulfide or thiosulfate. Some microorganisms can also use methionine or Cysteine-derived compounds such as glutathione as sole sulfur source. Glutathione is degraded to liberate Cysteine, whereas methionine is converted into Cysteine via the reverse transsulfuration pathway or via methanethiol formation. Cysteine is also taken up directly from the environment by ABC transporters or symporters mainly as cystine, the disulfide-linked Cysteine dimer. Several mechanisms are involved in the control of the intracellular concentration of Cysteine, which is a highly reactive compound due to its –SH group. This amino acid is degraded mainly by Cysteine desulfhydrases or is excreted by exporters. A large variety of molecular mechanisms participate in fine-tuning the regulation of Cysteine Metabolism: positive regulation by LysR-type regulators, negative control by repressors of the Rrf2 or TetR family and regulation by premature termination of transcription. In Escherichia coli and Bacillus subtilis, a global regulator, CysB and CymR, respectively, controls Cysteine synthesis and transport in response to O-acetylserine or its derivative N-acetyl-serine availability. In Lactococcus lactis and Corynebacterium glutamicum, a unique regulator modulates the methionine and Cysteine Metabolisms. Cysteine or derivative compounds are biotechnically interesting. Fermentation processes with E. coli or C. glutamicum involving mutants insensitive to feedback inhibition by Cysteine and also strains overproducing Cysteine exporters or inactivated for Cysteine degradative enzymes are currently being developed.
Deborah L Bella - One of the best experts on this subject based on the ideXlab platform.
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Cysteine Metabolism in periportal and perivenous hepatocytes perivenous cells have greater capacity for glutathione production and taurine synthesis but not for Cysteine catabolism
Amino Acids, 2002Co-Authors: Deborah L Bella, Young Hye Kwon, Lawrence L Hirschberger, Martha H StipanukAbstract:Hepatocyte preparations highly enriched in cells from either the periportal or the perivenous zone of the liver acinus were prepared using a digitonin/collagenase perfusion method. Five enzymes of Cysteine Metabolism were assayed in both periportal and perivenous preparations. The ratios of periportal to perivenous activity were 0.76, 0.60, 0.81, 1.62, and 1.01 for Cysteine dioxygenase, Cysteinesulfinate decarboxylase, γ-glutamylCysteine synthetase, cystathionase, and asparate (Cysteinesulfinate) aminotransferase, respectively. Only Cysteinesulfinate decarboxylase activity was significantly different between periportal and perivenous cells. In incubations with 2 mmol/L [35S]Cysteine, total Cysteine catabolism ([35S]taurine plus [35S]sulfate) between periportal and perivenous cells was not different, which is consistent with the observation of similar Cysteine dioxygenase activity across the hepatic acinus. Consistent with the lower Cysteinesulfinate decarboxylase activity in periportal cells, 16% of the total catabolism of [35S]Cysteine in periportal cells resulted in taurine synthesis compared to 28% in perivenous cells. A lower rate of [35S]glutathione synthesis was observed in periportal cells compared to perivenous cells, but γ-glutamylCysteine synthetase activity was not significantly different between perivenous and periportal cells. Cysteinesulfnate decarboxylase can be added to the list of enzymes whose activities are markedly enriched in perivenous cells.
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effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of Cysteine Metabolism
American Journal of Physiology-endocrinology and Metabolism, 1999Co-Authors: Deborah L Bella, Christine Hahn, Martha H StipanukAbstract:To determine the role of nonsulfur vs. sulfur amino acids in regulation of Cysteine Metabolism, rats were fed a basal diet or diets supplemented with a mixture of nonsulfur amino acids (AA), sulfur...
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mechanisms involved in the regulation of key enzymes of Cysteine Metabolism in rat liver in vivo
American Journal of Physiology-endocrinology and Metabolism, 1999Co-Authors: Deborah L Bella, Lawrence L Hirschberger, Yu Hosokawa, Martha H StipanukAbstract:Little is known about mechanisms of regulation of Cysteine dioxygenase (CDO), γ-glutamylCysteine synthetase (GCS), and Cysteine-sulfinate decarboxylase (CSDC) in response to diet. Enzyme activity and Western and Northern or dot blot analyses were conducted on liver samples from rats fed a basal low-protein diet or diets with graded levels of protein or methionine for 2 wk. Higher levels of CDO activity and CDO protein but not of CDO mRNA were observed in liver of rats fed methionine or protein-supplemented diets, indicating that CDO activity is regulated by changes in enzyme concentration. Lower concentrations of the heavy or catalytic subunit of GCS (GCS-HS) mRNA and protein, as well as a lower activity state of GCS-HS in rats fed methionine- or protein-supplemented diets, indicated that dietary regulation of GCS occurs by both pretranslational and posttranslational mechanisms. Lower CSDC activity, CSDC protein concentration, and CSDC mRNA concentration were found in rats fed the highest level of protein...
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variations in dietary protein but not in dietary fat plus cellulose or carbohydrate levels affect Cysteine Metabolism in rat isolated hepatocytes
Journal of Nutrition, 1996Co-Authors: Deborah L Bella, Young Hye Kwon, Martha H StipanukAbstract:: To determine if previously observed effects of dietary protein on hepatic Cysteine Metabolism were due specifically to increases in dietary protein or to the accompanying decreases in dietary carbohydrate, two experiments were conducted. In one experiment, rats were fed diets that contained different levels of protein vs. an isocaloric mixture of fat + cellulose and a constant amount of carbohydrate. In the other, rats were fed diets that contained a constant amount of protein but different levels of carbohydrate vs. an isocaloric mixture of fat+cellulose. Diets were fed for 2-3 wk and hepatocytes were then isolated. Hepatic Cysteine dioxygenase activity increased and Cysteinesulfinate decarboxylase and gamma-glutamylCysteine synthetase activities decreased in a stepwise manner when protein was added to the diet at the expense of fat + cellulose. Changes in Cysteine dioxygenase, Cysteinesulfinate decarboxylase and gamma-glutamylCysteine synthetase activities were consistent with changes in rates of Cysteine catabolism, taurine production and glutathione synthesis, respectively, by intact hepatocytes incubated with 0.2 mmol/L Cysteine. When the carbohydrate to fat+ cellulose ratio was varied, but the protein level was held constant, little or no change in enzyme activities or levels of metabolite production was observed. Regulation of the activities of enzymes involved in Cysteine Metabolism is predominantly due to changes in dietary protein intake and not to the associated changes in intake of other dietary macronutrients.
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high levels of dietary protein or methionine have different effects on Cysteine Metabolism in rat hepatocytes
Advances in Experimental Medicine and Biology, 1996Co-Authors: Deborah L Bella, Martha H StipanukAbstract:Cysteine catabolism in mammalian liver can occur by both Cysteine sulfinate-dependent and Cysteine sulfinate-independent pathways. Both pathways lead to the production of pyruvate and sulfate, but only the Cysteine sulfinate-dependent pathway leads to taurine production. Cysteine dioxygenase (CDO; EC 1.13.11.20) catalyzes the first reaction in the Cysteine sulfinate-dependent catabolic pathway, by which Cysteine is oxidized to Cysteine sulfinate. Cysteine sulfinate has two possible catabolic fates. It can be transaminated by aspartate aminotransferase (AAT; EC 2.6.1.1) which ultimately yields pyruvate and sulfate, or it can be decarboxylated by Cysteine sulfinate decarboxylase (CSAD; EC 4.1.1.29) to hypotaurine. Hypotaurine is then presumably non-enzymatically oxidized to taurine. Both taurine and sulfate are important metabolites required by the body for essential functions as well as being end-products of Cysteine catabolism that are excreted in the urine.
Yong Ye - One of the best experts on this subject based on the ideXlab platform.
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a fret based ratiometric fluorescent probe to detect Cysteine Metabolism in mitochondria
Organic and Biomolecular Chemistry, 2020Co-Authors: Zhiyao Zhai, Xiaopeng Yang, Di Zhang, Jun Tang, Yong YeAbstract:As an important biothiol in living cells, Cysteine is closely related to oxidative damage in living organisms. Sulfite from Cysteine Metabolism in living cells plays a crucial role in maintaining homeostasis in an organism, and the unbalance of sulfite in vivo would lead to multiple diseases. Thus the development of a new fluorescent probe for Cysteine Metabolism is needed urgently in mitochondria which are the main place of Cysteine Metabolism. Herein we construct a novel targeting mitochondria fluorescent probe CP-K based on the FRET mechanism to visualize sulfite in living MCF-7 cells. Probe CP-K displays a large Stokes shift of 150 nm, a low detection limit (26.3 nM) and “naked eye” detection after the addition of HSO3−. Importantly, it is appropriate for imaging the endogenous sulfite from Cysteine Metabolism in living cells.
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a multi signal mitochondria targeted fluorescent probe for real time visualization of Cysteine Metabolism in living cells and animals
Chemical Communications, 2018Co-Authors: Xiaopeng Yang, Jun Tang, Yong Ye, Ping Li, Haibo Weng, Ming Xian, Bo Tang, Yufen ZhaoAbstract:In this study, we developed a multi-signal mitochondria-targeted fluorescent probe (NIR-Cys) for simultaneous detection of Cys and its metabolite, SO2. In the design of the probe, the acrylate group and the CC of the coumarin ring were used as the recognizing moiety for Cys and SO2, respectively. The probe exhibited high sensitivity, excellent specificity, and fast response. NIR-Cys was found to precisely target and visualize Cys Metabolism in mitochondria of living cells with a multi-fluorescence signal. This probe is expected to be a useful tool for understanding Cys Metabolism.
