Abstract Respiratory complex II succinate: Complex II mutations have been linked to neurodegenerative diseases and metabolic defects in cancer.
The quinone ring is surrounded by Ile28 of subunit C and Pro of subunit B. These residuesalong with Il, Trp, and Trp of subunit B, and Ser27 C atom of subunit C, form the hydrophobic environment of the quinone -binding pocket not shown in the image.
The side chains Thr, His, and Arg of subunit A stabilize the molecule while FAD oxidizes and carries the electrons to the first of the iron-sulfur clusters[2Fe-2S]. Redox centers[ edit ] The succinate -binding site and ubiquinone -binding site are connected by a chain of redox centers including FAD and the iron - sulfur clusters.
E2 Succinate oxidation mechanism.
E1cb Succinate oxidation mechanism. Succinate oxidation[ edit ] Little is known about the exact succinate oxidation mechanism. However, the crystal structure shows that FADGlu, Arg, and His of subunit A not shown are good candidates for the initial deprotonation step.
Thereafter, there are two possible elimination mechanisms: In the E2 elimination, the mechanism is concerted. The basic residue or cofactor deprotonates the alpha carbonand FAD accepts the hydride from the beta carbonoxidizing the bound succinate to fumarate —refer to image 6.
In E1cb, an enolate intermediate is formed, shown in image 7, before FAD accepts the hydride. Further research is required to determine which elimination mechanism succinate undergoes in Succinate Dehydrogenase.
Oxidized fumaratenow loosely bound to the active siteis free to exit the protein. Electron tunneling[ edit ] After the electrons are derived from succinate oxidation via FADthey tunnel along the [Fe-S] relay until they reach the [3Fe-4S] cluster.
These electrons are subsequently transferred to an awaiting ubiquinone molecule within the active site. The Iron - Sulfur electron tunneling system is shown in image 9. Electron carriers of the SQR complex. FADH2, iron-sulfur centers, heme b, and ubiquinone.
The O1 carbonyl oxygen of ubiquinone is oriented at the active site image 4 by hydrogen bond interactions with Tyr83 of subunit D. The presence of electrons in the [3Fe-4S] iron sulphur cluster induces the movement of ubiquinone into a second orientation.
This facilitates a second hydrogen bond interaction between the O4 carbonyl group of ubiquinone and Ser27 of subunit C. Following the first single electron reduction step, a semiquinone radical species is formed.
The second electron arrives from the [3Fe-4S] cluster to provide full reduction of the ubiquinone to ubiquinol. This mechanism of the ubiquinone reduction is shown in image 8. Heme prosthetic group[ edit ] Although the functionality of the heme in succinate dehydrogenase is still being researched, some studies[ by whom?
In this way, the heme cofactor acts as an electron sink. Its role is to prevent the interaction of the intermediate with molecular oxygen to produce reactive oxygen species ROS. The heme group, relative to ubiquinoneis shown in image 4.
It has also been proposed that a gating mechanism may be in place to prevent the electrons from tunneling directly to the heme from the [3Fe-4S] cluster. A potential candidate is residue His, which lies directly between the cluster and the heme. His of subunit B is in direct proximity to the [3Fe-4S] cluster, the bound ubiquinoneand the heme ; and could modulate electron flow between these redox centers.
The semiquinone species is protonated by protons delivered from HOH39, completing the ubiquinone reduction to ubiquinol. His and Asp82 most likely facilitate this process. Other studies claim that Tyr83 of subunit D is coordinated to a nearby histidine as well as the O1 carbonyl oxygen of ubiquinone.
The histidine residue decreases the pKa of tyrosinemaking it more suitable to donate its proton to the reduced ubiquinone intermediate.
Inhibitors[ edit ] There are two distinct classes of inhibitors of complex II:Succinate is the substrate, and fumarate is the product Succinate dehydrogenase catalyzes the conversion of succinate to fumarate.
The reaction is inhibited by malonic acid, which resembles succinate but cannot be acted upon by succinate dehydrogenase.
Nov 01, · A spectrophotometric coupled enzyme assay to measure the activity of succinate dehydrogenase the reaction with ubiquinol is inefficient, electrons are not scavenged stoichiometrically when the respiratory chain is turning over, and the measured rate is always a combination of all possible pathways.
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An Experiment to Determine the Rate of Reaction of Succinate to Fumerate. 1, words. 8 pages. Radiation and Ionizing and Non-Ionizing Classification and Their Effects. 1, words. 4 pages.
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4, words. 16 pages. This experiment attempts to answer the question of whether an increase in a succinate concentration (a component of the Krebs cycle) will lead to an increased rate of cellular respiration within a cell.
We measured the amount of electrons given off by the succinate to fumerate redox reaction by using DPIP. (Wrischnik, ). One way to. You will determine the activity of the enzyme in each fraction by relating the oxidation of succinate by succinate deydrogenase to a decrease in absorbance resulting from the reduction of DCIP.