Mechanism Succinate dehydrogenase

1 mechanism

1.1 succinate oxidation
1.2 electron tunneling
1.3 ubiquinone reduction
1.4 heme prosthetic group
1.5 proton transfer

mechanism

image 6: e2 succinate oxidation mechanism.



image 7: e1cb succinate oxidation mechanism.


succinate oxidation

little known exact succinate oxidation mechanism. however, crystal structure shows fad, glu255, arg286, , his242 of subunit (not shown) candidates initial deprotonation step. thereafter, there 2 possible elimination mechanisms: e2 or e1cb. in e2 elimination, mechanism concerted. basic residue or cofactor deprotonates alpha carbon, , fad accepts hydride beta carbon, oxidizing bound succinate fumarate—refer image 6. in e1cb, enolate intermediate formed, shown in image 7, before fad accepts hydride. further research required determine elimination mechanism succinate undergoes in succinate dehydrogenase. oxidized fumarate, loosely bound active site, free exit protein.

electron tunneling

after electrons derived succinate oxidation via fad, tunnel along [fe-s] relay until reach [3fe-4s] cluster. these electrons subsequently transferred awaiting ubiquinone molecule within active site. iron-sulfur electron tunneling system shown in image 9.

ubiquinone reduction

image 8: ubiquinone reduction mechanism.



image 9: electron carriers of sqr complex. fadh2, iron-sulfur centers, heme b, , ubiquinone.

the o1 carbonyl oxygen of ubiquinone oriented @ active site (image 4) hydrogen bond interactions tyr83 of subunit d. presence of electrons in [3fe-4s] iron sulphur cluster induces movement of ubiquinone second orientation. facilitates second hydrogen bond interaction between o4 carbonyl group of ubiquinone , ser27 of subunit c. following first single electron reduction step, semiquinone radical species formed. second electron arrives [3fe-4s] cluster provide full reduction of ubiquinone ubiquinol. mechanism of ubiquinone reduction shown in image 8.

heme prosthetic group

although functionality of heme in succinate dehydrogenase still being researched, studies have asserted first electron delivered ubiquinone via [3fe-4s] may tunnel , forth between heme , ubiquinone intermediate. in way, heme cofactor acts electron sink. role prevent interaction of intermediate molecular oxygen produce reactive oxygen species (ros). heme group, relative ubiquinone, shown in image 4.

it has been proposed gating mechanism may in place prevent electrons tunneling directly heme [3fe-4s] cluster. potential candidate residue his207, lies directly between cluster , heme. his207 of subunit b in direct proximity [3fe-4s] cluster, bound ubiquinone, , heme; , modulate electron flow between these redox centers.

proton transfer

to reduce quinone in sqr, 2 electrons 2 protons needed. has been argued water molecule (hoh39) arrives @ active site , coordinated his207 of subunit b, arg31 of subunit c, , asp82 of subunit d. semiquinone species protonated protons delivered hoh39, completing ubiquinone reduction ubiquinol. his207 , asp82 facilitate process. other studies claim tyr83 of subunit d coordinated nearby histidine o1 carbonyl oxygen of ubiquinone. histidine residue decreases pka of tyrosine, making more suitable donate proton reduced ubiquinone intermediate.