Enzymology of Sulfide Oxidation
硫化物氧化的酶学
基本信息
- 批准号:9313289
- 负责人:
- 金额:$ 29.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-01 至 2019-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAortaApoptosisAtaxiaBacteriaBiochemicalBiogenesisBiologicalBloodBlood VesselsCatabolismCell RespirationCellsCellular Stress ResponseClinicalColorectal CancerConsumptionCoupledCouplesCyanidesCystathionineCysteineCysteine DesulfhydraseDataDefectDevelopmental Delay DisordersDioxygenasesDiseaseElectron TransportEncephalopathiesEnzymatic BiochemistryEnzymesErythrocytesEventExcisionExhibitsFailureFoundationsGasesGenerationsGlutathioneGoalsHealthHemoglobinHemorrhagic colitisHomeostasisHumanHydrogen SulfideHypoxiaInflammationKineticsLaboratoriesLeadLiteratureMammalsMediatingMetabolicMetabolismMethemoglobinMethodsMitochondriaMolecularMutationNADPNeurologicOrganismOxidative PhosphorylationOxidoreductaseOxygenPathway interactionsPetechiaePharmacologic SubstancePhysiologicalPlasmaPopulationPredispositionProcessProductionProteinsQuinonesReactionReactive Oxygen SpeciesRegulationReportingRoleRouteSignal TransductionSignaling MoleculeSulfidesSulfitesSulfurSulfur Metabolism PathwayTXN geneTherapeuticThiosulfate SulfurtransferaseTissuesToxic effectTwin Multiple BirthUlcerative ColitisUncertaintyUnspecified or Sulfate Ion SulfatesVariantWidthcellular targetingcytochrome c oxidasedesignenzyme pathwaymanneuroregulationnoveloxidationpersulfidespublic health relevanceresponsesulfite oxidasesulfurtransferasethioredoxin reductase
项目摘要
DESCRIPTION (provided by applicant): Hydrogen sulfide (H2S), a signaling molecule that elicits profound physiological effects, is a product of mammalian sulfur metabolism and is synthesized at relatively high rates. Since H2S is highly toxic, cells avoid its build-up by an efficient oxidation pathway that is housed in mitochondria and coupled to the energy-generating electron transport chain. The constituent proteins include sulfide-quinone oxidoreductase (SQR), a persulfide dioxygenase (ETHE1) and rhodanese in addition to the well-studied sulfite oxidase that catalyzes the conversion of sulfite to sulfate in the terminal step in the pathway. In
red blood cells on the other hand, which exhibit robust H2S production capacity but lack mitochondria and hence the classical route for sulfide oxidation, the mechanism of sulfide clearance is unknown. In this study, we propose to address fundamental gaps in our understanding of the oxygen-dependent steps catalyzed by SQR and ETHE1, which combine to maintain low steady-state levels of H2S (in the 10-30 nM range in most tissues) and to elucidate the role of rhodanese in the sulfide oxidation pathway. We also propose to elucidate the potential role of methemoglobin in sulfide removal in red blood cells. These goals will be realized by addressing the following specific aims. (i) Using a combination of spectroscopic and kinetic methods we will elucidate the reaction mechanisms of human SQR and ETHE1. (ii) We will assess the relative catalytic efficiencies with which rhodanese generates glutathione persulfide, thiosulfate and H2S and elucidate the biochemical differences between two common polymorphic rhodanese variants. (iii) We will elucidate the mechanism of methemoglobin-dependent sulfide oxidation and assess its contribution to sulfide clearance at physiologically relevant concentrations of H2S and methemoglobin. Our studies will address fundamental questions such as how the sulfide oxidation pathway is wired, elucidate the reaction mechanisms of key enzymes that are potentially important pharmaceutical targets for modulating H2S levels and assess a novel and previously unexplored role for human hemoglobin in maintaining low plasma H2S concentrations.
描述(由申请人提供):硫化氢(H2S)是一种信号分子,具有深远的生理作用,是哺乳动物硫代谢的产物,合成速率相对较高。由于H2S是剧毒的,细胞通过一个有效的氧化途径来避免H2S的积累,这个氧化途径位于线粒体中,并与产生能量的电子传递链相结合。其组成蛋白包括硫化物-醌氧化还原酶(SQR)、过硫双加氧酶(ETHE1)和罗丹斯酶,以及在该途径的最后一步催化亚硫酸盐转化为硫酸盐的亚硫酸盐氧化酶。在
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Modulation of Catalytic Promiscuity during Hydrogen Sulfide Oxidation.
- DOI:10.1021/acschembio.8b00258
- 发表时间:2018-06-15
- 期刊:
- 影响因子:4
- 作者:Landry AP;Ballou DP;Banerjee R
- 通讯作者:Banerjee R
Sulfide oxidation by a noncanonical pathway in red blood cells generates thiosulfate and polysulfides.
红细胞中的硫化物通过非典型途径氧化产生硫代硫酸盐和多硫化物。
- DOI:10.1074/jbc.m115.639831
- 发表时间:2015
- 期刊:
- 影响因子:0
- 作者:Vitvitsky,Victor;Yadav,PramodK;Kurthen,Angelika;Banerjee,Ruma
- 通讯作者:Banerjee,Ruma
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RUMA V BANERJEE其他文献
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{{ truncateString('RUMA V BANERJEE', 18)}}的其他基金
The Sulfur/Glutamate Circuitry in the Neuroimmune System
神经免疫系统中的硫/谷氨酸回路
- 批准号:
7782403 - 财政年份:2009
- 资助金额:
$ 29.34万 - 项目类别:
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