Q cycle
Encyclopedia
History
The Q cycle describes a series of reactions first proposed by Peter Mitchell that describe how the sequential oxidation and reduction of the lipophilic electron carrier, ubiquinolUbiquinol
Ubiquinol is an electron-rich form of coenzyme Q10.The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side chain is 9-10 units long in mammals...
-ubiquinone (a.k.a. Coenzyme Q), can result in the net pumping of protons across a lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
bilayer (in the case of mitochondria, the inner mitochondrial membrane). A modified version of Mitchell's original scheme is now accepted as the mechanism by which Complex III pumps protons (i.e. how complex III contributes to the biochemical generation of the proton or pH, gradient, which is used for the biochemical generation of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
)..
Process
Operation of the modified Q cycle in Complex III results in the reduction of Cytochrome cCytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, oxidation of ubiquinol
Ubiquinol
Ubiquinol is an electron-rich form of coenzyme Q10.The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side chain is 9-10 units long in mammals...
to ubiquinone, and the transfer of four protons into the intermembrane space, per two-cycle process.
Ubiquinol (QH2) binds to the Qo site of complex III via hydrogen bonding to His182 of the Rieske iron-sulfur protein
Rieske protein
Rieske proteins are iron-sulfur protein components of cytochrome bc1 complexes and cytochrome b6f complexes which were first discovered and isolated by John S. Rieske and co-workers in 1964. It is a unique [2Fe-2S] cluster in that one of the two Fe atoms is coordinated by two histidine residues...
and Glu272 of Cytochrome b
Cytochrome b
Cytochrome b/b6 is the main subunit of transmembrane cytochrome bc1 and b6f complexes. In addition, it commonly refers to a region of mtDNA used for population genetics and phylogenetics.- Function :...
. Ubiquinone (Q), in turn, binds the Qi site of complex III. Ubiquinol is divergently oxidized (gives up one electron each) to the Rieske iron-sulfur '(FeS) protein'
Rieske protein
Rieske proteins are iron-sulfur protein components of cytochrome bc1 complexes and cytochrome b6f complexes which were first discovered and isolated by John S. Rieske and co-workers in 1964. It is a unique [2Fe-2S] cluster in that one of the two Fe atoms is coordinated by two histidine residues...
and to the bL heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
. This oxidation reaction produces a transient semiquinone before complete oxidation to ubiquinone, which then leaves the Qo site of complex III.
Having acquired one electron from ubiquinol, the 'FeS protein' is freed from its electron donor and is able to migrate to the Cytochrome c1 subunit. 'FeS protein' then donates its electron to Cytochrome c1, reducing its bound heme group. The electron is from there transferred to an oxidized molecule of Cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
externally bound to complex III, which then dissociates from the complex. In addition, the reoxidation of the 'FeS protein' releases the proton bound to His181 into the intermembrane space.
The other electron, which was transferred to the bL heme, is used to reduce the bH heme, which in turn transfers the electron to the ubiquinone bound at the Qi site. The attached ubiquinone is thus reduced to a semiquinone
Semiquinone
Semiquinone is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone to quinone or alternatively the addition of a single H atom to a quinone....
radical. The proton taken up by Glu272 is subsequently transferred to a hydrogen-bonded water chain as Glu272 rotates 170° to hydrogen bond a water molecule, in turn hydrogen-bonded to a propionate
Propionate
The propanoate or propionate ion is C2H5COO− .A propanoic or propionic compound is a salt or ester of propanoic acid....
of the bL heme.
Because the last step leaves an unstable semiquinone
Semiquinone
Semiquinone is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone to quinone or alternatively the addition of a single H atom to a quinone....
at the Qi site, the reaction is not yet fully completed. A second Q cycle is necessary, with the second electron transfer from cytochrome bH reducing the semiquinone to ubiquinol. The ultimate products of the Q cycle are four protons entering the intermembrane space, two protons taken up from the matrix and the reduction of two molecules of cytochrome c. The reduced cytochrome c is eventually reoxidized by complex IV. The process is cyclic as the ubiquinone created at the Qi site can be reused by binding to the Qo site of complex III.