The water channel of cytochrome c oxidase: inferences from inhibitor studies.
Cytochrome c oxidase couples electron transfer to proton transfer from inside the mitochondrion to the cytosol. Protons pass through a channel; it is closed except when protons are pumped. Electron transfer is also coupled to a water cycle. Water moves into and out of the oxidase during electron transfer, presumably through a channel. The three processes are coupled because of the common dependence on electron transfer. If water and protons had to pass through the same channel for the proton to pass, it might be possible to block the pore by entraining small molecules in the flow. The data in this report indicate that there is a correlation between the ability of a compound to inhibit the oxidase and its size. Formamide and formaldehyde are potent inhibitors. Larger and smaller molecules are poor inhibitors. Formamide introduces an internal block in electron transfer. It is a slow-onset, reversible inhibitor, dependent on turnover to manifest its effects. Vesicular oxidase is less influenced by formamide than is soluble oxidase; formamide must pass a permeability barrier to act. The data are consistent with a proton channel with constrictions at both ends that open to yield a pore of approximately 4 A.
Kornblatt
J A
JA
Enzyme Research Group, Department of Biology, Concordia University, Montréal, Québec H3G 1M8, Canada. krnbltt@vax2.concordia.ca
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D005559:Formamides / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011522:Protons; D014867:Water / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005559:Formamides; D007473:Ion Channels; D011522:Protons; D014867:Water; D005557:Formaldehyde; C031066:formamide; D003576:Electron Transport Complex IV