• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

在琥珀酸脱氢酶/SDHB 亚复合物中，以反醌-富马酸盐还原酶方向进行 ROS 产生和二极管样行为的数学建模。

Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction.

机构信息

Institute of Theoretical and Experimental Biophysics of RAS, 142290 Pushchino, Russia.

Institute of Cell Biophysics of RAS, 142290 Pushchino, Russia.

出版信息

Int J Mol Sci. 2022 Dec 9;23(24):15596. doi: 10.3390/ijms232415596.

DOI:10.3390/ijms232415596
PMID:36555239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9778801/
Abstract

Succinate dehydrogenase (SDH) plays an important role in reverse electron transfer during hypoxia/anoxia, in particular, in ischemia, when blood supply to an organ is disrupted, and oxygen is not available. It was detected in the voltammetry studies about three decades ago that the SDHA/SDHB subcomplex of SDH can have such a strong nonlinear property as a "tunnel-diode" behavior in reverse quinol-fumarate reductase direction. The molecular and kinetic mechanisms of this phenomenon, that is, a strong drop in the rate of fumarate reduction as the driving force is increased, are still unclear. In order to account for this property of SDH, we developed and analyzed a mechanistic computational model of reverse electron transfer in the SDHA/SDHB subcomplex of SDH. It was shown that a decrease in the rate of succinate release from the active center during fumarate reduction quantitatively explains the experimentally observed tunnel-diode behavior in SDH and threshold values of the electrode potential of about -80 mV. Computational analysis of ROS production in the SDHA/SDHB subcomplex of SDH during reverse electron transfer predicts that the rate of ROS production decreases when the tunnel-diode behavior appears. These results predict a low rate of ROS production by the SDHA/SDHB subcomplex of SDH during ischemia.

摘要

琥珀酸脱氢酶 (SDH) 在缺氧/无氧期间的逆向电子转移中发挥重要作用，特别是在缺血期间，当器官的血液供应中断且无法获得氧气时。大约三十年前的伏安法研究中检测到，SDH 的 SDHA/SDHB 亚基在逆向醌-富马酸还原酶方向上具有如此强烈的非线性特性，即“隧道二极管”行为。这种现象的分子和动力学机制，即随着驱动力的增加，富马酸还原率的强烈下降，仍然不清楚。为了解释 SDH 的这种特性，我们开发并分析了 SDH 的 SDHA/SDHB 亚基中逆向电子转移的机制计算模型。结果表明，富马酸还原过程中从活性中心释放琥珀酸的速率降低，定量解释了 SDH 中实验观察到的隧道二极管行为和电极电势的阈值约为-80 mV。在逆向电子转移过程中对 SDH 的 SDHA/SDHB 亚基中 ROS 生成的计算分析预测，当出现隧道二极管行为时，ROS 生成的速率会降低。这些结果预测了在缺血期间 SDH 的 SDHA/SDHB 亚基产生 ROS 的速率较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/5d16ecbd92a5/ijms-23-15596-g010a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/d81e57465f99/ijms-23-15596-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/43037d010456/ijms-23-15596-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/c6e4a279ce9b/ijms-23-15596-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/73d00f11931c/ijms-23-15596-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/e3862c5f5863/ijms-23-15596-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/51c73cde63ef/ijms-23-15596-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/2ba8a58a623e/ijms-23-15596-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/86c9bd8ad311/ijms-23-15596-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/666918cf9f4d/ijms-23-15596-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/5d16ecbd92a5/ijms-23-15596-g010a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/d81e57465f99/ijms-23-15596-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/43037d010456/ijms-23-15596-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/c6e4a279ce9b/ijms-23-15596-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/73d00f11931c/ijms-23-15596-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/e3862c5f5863/ijms-23-15596-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/51c73cde63ef/ijms-23-15596-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/2ba8a58a623e/ijms-23-15596-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/86c9bd8ad311/ijms-23-15596-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/666918cf9f4d/ijms-23-15596-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/9778801/5d16ecbd92a5/ijms-23-15596-g010a.jpg

相似文献

1
Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction.在琥珀酸脱氢酶/SDHB 亚复合物中，以反醌-富马酸盐还原酶方向进行 ROS 产生和二极管样行为的数学建模。
Int J Mol Sci. 2022 Dec 9;23(24):15596. doi: 10.3390/ijms232415596.
2
Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II.在线粒体呼吸复合物 II 中逆向电子转移期间延胡索酸还原酶活性和 ROS 产生的动力学的计算建模分析。
Int J Mol Sci. 2023 May 5;24(9):8291. doi: 10.3390/ijms24098291.
3
Essentiality of succinate dehydrogenase in Mycobacterium smegmatis and its role in the generation of the membrane potential under hypoxia.耻垢分枝杆菌中琥珀酸脱氢酶的必要性及其在缺氧条件下膜电位产生中的作用。
mBio. 2014 Aug 12;5(4):e01093-14. doi: 10.1128/mBio.01093-14.
4
Potential Pitfalls of SDH Immunohistochemical Detection in Paragangliomas and Phaeochromocytomas Harbouring Germline Gene Mutation.伴有胚系基因突变的副神经节瘤和嗜铬细胞瘤中SDH免疫组化检测的潜在陷阱
Anticancer Res. 2017 Feb;37(2):805-812. doi: 10.21873/anticanres.11381.
5
Classification of fumarate reductases and succinate dehydrogenases based upon their contrasting behaviour in the reduced benzylviologen/fumarate assay.基于富马酸还原酶和琥珀酸脱氢酶在还原苄基紫精/富马酸测定中相反行为的分类
FEBS Lett. 1993 Jul 12;326(1-3):92-4. doi: 10.1016/0014-5793(93)81768-u.
6
Identification of succinate dehydrogenase-deficient bladder paragangliomas.鉴定琥珀酸脱氢酶缺陷型膀胱副神经节瘤。
Am J Surg Pathol. 2013 Oct;37(10):1612-8. doi: 10.1097/PAS.0b013e318293d83c.
7
Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST.KIT/PDGFRA野生型胃肠道间质瘤中琥珀酸脱氢酶复合物所有亚基SDHA、SDHB、SDHC、SDHD的分析
Eur J Hum Genet. 2014 Jan;22(1):32-9. doi: 10.1038/ejhg.2013.80. Epub 2013 Apr 24.
8
Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis.复合物II的SdhB亚基而非SdhA亚基的缺失会触发活性氧依赖性缺氧诱导因子激活和肿瘤发生。
Mol Cell Biol. 2008 Jan;28(2):718-31. doi: 10.1128/MCB.01338-07. Epub 2007 Oct 29.
9
Succinate dehydrogenase (SDH)-deficient neoplasia.琥珀酸脱氢酶（SDH）缺陷型肿瘤。
Histopathology. 2018 Jan;72(1):106-116. doi: 10.1111/his.13277.
10
Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors.SDHA 表达缺失可鉴定琥珀酸脱氢酶缺陷型胃肠道间质瘤中的 SDHA 突变。
Am J Surg Pathol. 2013 Feb;37(2):226-33. doi: 10.1097/PAS.0b013e3182671155.

引用本文的文献

1
Metabolomic and Proteomic Analyses Unveil That Polyethylene Glycol-Polycaprolactone-Loaded Curcumin Nanoparticles Induce Mitochondrial Dysfunction and Metabolic Reprogramming to Suppress Melanoma Growth.代谢组学和蛋白质组学分析揭示，负载聚乙二醇-聚己内酯的姜黄素纳米颗粒可诱导线粒体功能障碍和代谢重编程以抑制黑色素瘤生长。
ACS Appl Mater Interfaces. 2025 Jun 11;17(23):33422-33438. doi: 10.1021/acsami.5c02854. Epub 2025 May 27.
2
Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II.在线粒体呼吸复合物 II 中逆向电子转移期间延胡索酸还原酶活性和 ROS 产生的动力学的计算建模分析。
Int J Mol Sci. 2023 May 5;24(9):8291. doi: 10.3390/ijms24098291.

本文引用的文献

1
Fumarate is a terminal electron acceptor in the mammalian electron transport chain.延胡索酸盐是哺乳动物电子传递链中的末端电子受体。
Science. 2021 Dec 3;374(6572):1227-1237. doi: 10.1126/science.abi7495. Epub 2021 Dec 2.
2
Computational Modeling Analysis of Generation of Reactive Oxygen Species by Mitochondrial Assembled and Disintegrated Complex II.线粒体组装和解离的复合物II产生活性氧的计算模型分析
Front Physiol. 2020 Oct 16;11:557721. doi: 10.3389/fphys.2020.557721. eCollection 2020.
3
Computationally modeling mammalian succinate dehydrogenase kinetics identifies the origins and primary determinants of ROS production.
通过计算模拟哺乳动物琥珀酸脱氢酶动力学，确定了 ROS 产生的起源和主要决定因素。
J Biol Chem. 2020 Nov 6;295(45):15262-15279. doi: 10.1074/jbc.RA120.014483. Epub 2020 Aug 28.
4
Hysteresis and bistability in the succinate-CoQ reductase activity and reactive oxygen species production in the mitochondrial respiratory complex II.琥珀酸-CoQ 还原酶活性和线粒体呼吸复合物 II 中活性氧产生的滞后和双稳现象。
Redox Biol. 2020 Oct;37:101630. doi: 10.1016/j.redox.2020.101630. Epub 2020 Jul 5.
5
Succinate in ischemia: Where does it come from?琥珀酸在缺血中的来源：它来自哪里？
Int J Biochem Cell Biol. 2019 Oct;115:105580. doi: 10.1016/j.biocel.2019.105580. Epub 2019 Aug 5.
6
Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.心脏缺血时琥珀酸的积累主要通过经典的克雷布斯循环活动发生。
Cell Rep. 2018 May 29;23(9):2617-2628. doi: 10.1016/j.celrep.2018.04.104.
7
Respiratory complex II: ROS production and the kinetics of ubiquinone reduction.呼吸复合物 II：ROS 产生和泛醌还原的动力学。
Biochim Biophys Acta Bioenerg. 2017 Feb;1858(2):109-117. doi: 10.1016/j.bbabio.2016.10.008. Epub 2016 Oct 31.
8
Computational modeling analysis of mitochondrial superoxide production under varying substrate conditions and upon inhibition of different segments of the electron transport chain.在不同底物条件下以及电子传递链不同部分受到抑制时线粒体超氧化物产生的计算模型分析。
Biochim Biophys Acta. 2015 Jun-Jul;1847(6-7):656-79. doi: 10.1016/j.bbabio.2015.04.005. Epub 2015 Apr 11.
9
Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.琥珀酸的缺血性积累通过线粒体活性氧控制再灌注损伤。
Nature. 2014 Nov 20;515(7527):431-435. doi: 10.1038/nature13909. Epub 2014 Nov 5.
10
Commemorating the 1913 Michaelis-Menten paper Die Kinetik der Invertinwirkung: three perspectives.纪念 1913 年迈克米伦-门坦论文《蔗糖酶的动力学：三种观点》。
FEBS J. 2014 Jan;281(2):435-63. doi: 10.1111/febs.12598. Epub 2013 Dec 13.