Succinate Dehydrogenase: Difference between revisions

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====Succinate oxidation====
====Succinate oxidation====
The exact mechanism for the oxidation of succinate to fumarate has not yet been elucidated. The initial deprotonation may be performed by FAD, Glu255, Arg286, or His242 of SdhA, and the following elimination may be a concerted E2 or E1cb elimination. In the concerted mechanism, the α-carbon is deprotonated by a base as FAD removes a hydride from the β-carbon; this is shown in image 1 [8].
The exact mechanism for the oxidation of succinate to fumarate has not yet been elucidated. The initial deprotonation may be performed by FAD, Glu255, Arg286, or His242 of SdhA, and the following elimination may be a concerted E2 or E1cb elimination. In the concerted mechanism, the α-carbon is deprotonated by a base as FAD removes a hydride from the β-carbon; this is shown in image 1 <ref>PMID:16950775</ref>.


[[Image:S.D.Oxidation_of_Succinate_E2.gif]]
[[Image:S.D.Oxidation_of_Succinate_E2.gif]]
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Image 1: Oxidation of succinate to fumarate through E2 elimination
Image 1: Oxidation of succinate to fumarate through E2 elimination


In the proposed E1cb mechanism, the deprotonation leads to the formation of an enolate intermediate; FAD then removes the hydride, as shown in Image 2 [8].
In the proposed E1cb mechanism, the deprotonation leads to the formation of an enolate intermediate; FAD then removes the hydride, as shown in Image 2 <ref>PMID:16950775</ref>.


[[Image:S.D.Oxidation_of_Succinate_E1cb.gif]]
[[Image:S.D.Oxidation_of_Succinate_E1cb.gif]]
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====Ubiquinone reduction====
====Ubiquinone reduction====
Ubiquinone is initially oriented in the active site such that the O1 carbonyl group interacts with Tyr83 of SdhD via hydrogen bonding. The electrons removed during the oxidation reaction are conveyed through the iron-sulfur clusters to 3Fe-4S; their presence on that cluster stimulates the substrate to reorient so that a second hydrogen bond between the O4 carbonyl group and Ser27 of SdhC may form. The electrons are transferred to the substrate individually, with the addition of the first producing a radical semiquinone and the second completing the reduction to ubiquinol. This mechanism is illustrated in image 3 [8].
Ubiquinone is initially oriented in the active site such that the O1 carbonyl group interacts with Tyr83 of SdhD via hydrogen bonding. The electrons removed during the oxidation reaction are conveyed through the iron-sulfur clusters to 3Fe-4S; their presence on that cluster stimulates the substrate to reorient so that a second hydrogen bond between the O4 carbonyl group and Ser27 of SdhC may form. The electrons are transferred to the substrate individually, with the addition of the first producing a radical semiquinone and the second completing the reduction to ubiquinol. This mechanism is illustrated in image 3 <ref>PMID:16950775</ref>.


[[Image:QuinoneMechanism.gif]]
[[Image:QuinoneMechanism.gif]]

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