Target type: molecularfunction
Catalysis of the reaction: 4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O. [RHEA:11436]
Cytochrome c oxidase (COX), also known as complex IV, is the terminal enzyme of the mitochondrial electron transport chain. It is responsible for catalyzing the reduction of molecular oxygen (O2) to water (H2O) while simultaneously oxidizing reduced cytochrome c, a heme protein. The energy released from this reaction is used to pump protons across the inner mitochondrial membrane, generating a proton gradient that drives ATP synthesis.
The molecular function of COX involves a complex series of electron transfer reactions between metal centers within the enzyme. The process begins with the binding of reduced cytochrome c to COX, delivering an electron to heme a. This electron is then passed through a series of metal centers: heme a3, CuB, and finally to molecular oxygen bound to heme a3.
The reduction of oxygen occurs in a stepwise manner. First, O2 is bound to the reduced heme a3 and CuB, forming a superoxide anion (O2-). Subsequently, four electrons are transferred from cytochrome c to the enzyme, reducing O2 to two molecules of water. This process involves several intermediate states, including peroxide and hydroxyl radicals.
The transfer of electrons from cytochrome c to oxygen is coupled to the pumping of protons from the mitochondrial matrix to the intermembrane space. This proton pumping is driven by the energy released from the oxidation-reduction reactions. The proton gradient established across the inner mitochondrial membrane is then used by ATP synthase to generate ATP, the main energy currency of the cell.
In summary, the molecular function of cytochrome c oxidase involves the following key steps:
1. Binding of reduced cytochrome c to COX.
2. Electron transfer from cytochrome c to heme a and subsequent transfer through the metal centers of the enzyme.
3. Reduction of oxygen to water.
4. Proton pumping across the inner mitochondrial membrane.
5. Generation of a proton gradient that drives ATP synthesis.'
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Protein | Definition | Taxonomy |
---|---|---|
Cytochrome c oxidase subunit 2 | A cytochrome c oxidase subunit 2 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P00403] | Homo sapiens (human) |
Cytochrome c oxidase subunit 2 | A cytochrome c oxidase subunit 2 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P00403] | Homo sapiens (human) |
Cytochrome c oxidase subunit 1 | A cytochrome c oxidase subunit 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P00395] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
celecoxib | organofluorine compound; pyrazoles; sulfonamide; toluenes | cyclooxygenase 2 inhibitor; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug | |
diclofenac | diclofenac : A monocarboxylic acid consisting of phenylacetic acid having a (2,6-dichlorophenyl)amino group at the 2-position. Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. | amino acid; aromatic amine; dichlorobenzene; monocarboxylic acid; secondary amino compound | antipyretic; drug allergen; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-narcotic analgesic; non-steroidal anti-inflammatory drug; xenobiotic |
flufenamic acid | flufenamic acid : An aromatic amino acid consisting of anthranilic acid carrying an N-(trifluoromethyl)phenyl substituent. An analgesic and anti-inflammatory, it is used in rheumatic disorders. Flufenamic Acid: An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16) | aromatic amino acid; organofluorine compound | antipyretic; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
indomethacin | indometacin : A member of the class of indole-3-acetic acids that is indole-3-acetic acid in which the indole ring is substituted at positions 1, 2 and 5 by p-chlorobenzoyl, methyl, and methoxy groups, respectively. A non-steroidal anti-inflammatory drug, it is used in the treatment of musculoskeletal and joint disorders including osteoarthritis, rheumatoid arthritis, gout, bursitis and tendinitis. Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. | aromatic ether; indole-3-acetic acids; monochlorobenzenes; N-acylindole | analgesic; drug metabolite; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; gout suppressant; non-steroidal anti-inflammatory drug; xenobiotic; xenobiotic metabolite |
rofecoxib | butenolide; sulfone | analgesic; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug | |
valdecoxib | isoxazoles; sulfonamide | antipyretic; antirheumatic drug; cyclooxygenase 2 inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug | |
tolfenamic acid | tolfenamic acid : An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 3-chloro-2-methylphenyl group. Tolfenamic acid is used specifically for relieving the pain of migraine. It also shows anticancer activity. tolfenamic acid: structure | aminobenzoic acid; organochlorine compound; secondary amino compound | EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; EC 2.7.1.33 (pantothenate kinase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |