Computationally modeling mammalian succinate dehydrogenase kinetics identifies the origins and primary determinants of ROS production
Neeraj Manhas, Quynh V. Duong, Pilhwa Lee, Joshua D. Richardson, John D. Robertson, Michael A. Moxley, Jason N. Bazil
Abstract
production is only significant when the enzyme is fully reduced, and fumarate is absent. Our simulations also reveal that the redox state of the quinone pool is the primary determinant of free radical production by SDH. In this study, we showed the importance of analyzing enzyme kinetics and associated side reactions in a consistent, quantitative, and biophysically detailed manner using a diverse set of experimental data to interpret and explain experimental observations from a unified perspective.
Topics & Concepts
Succinate dehydrogenaseRedoxSemiquinoneChemistryQuinoneFumarate reductaseElectron transport chainRespiratory chainIron–sulfur clusterElectron Transport Complex ICoenzyme Q – cytochrome c reductaseHydrogen peroxideDehydrogenaseKineticsReductaseBiochemistryMitochondrionEnzymeOrganic chemistryCytochrome cPhysicsQuantum mechanicsATP Synthase and ATPases ResearchMitochondrial Function and PathologyCoenzyme Q10 studies and effects