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Towards the mechanism of cell respiration

Researchers at the Institute of Biotechnology of the University of Helsinki have for the first time identified an internal electron transfer reaction that initiates the proton pump mechanism of the respiratory enzyme. These new results are published in the Thursday (April 6th) issue of Nature.

The functions of the lungs, the blood circulation, and the red blood cells in respiration are only an overture to the physicochemical reaction in the cells where oxygen is reduced to water. Oxygen consumption in cell respiration is a strictly controlled enzymatic reaction in the inner mitochondrial membrane. The respiratory enzyme cytochrome oxidase functions as a proton pump that transduces free energy from oxygen reduction to an electrochemical proton gradient, which is utilised by another enzyme to produce ATP, the cells’ general energy currency.

The results by the research group of academy professor Mårten Wikström revealed the coupling between the function of the proton pump and oxygen reduction: an internal electron transfer initiates the first stage of the pump mechanism. "This finding opens the door towards understanding the mechanism, which has been the subject of research for almost 30 years", Wikström says.

The proton pump of cytochrome oxidase is closely linked to the process by which the energy of foodstuffs is transduced into a useful energy source for our cells. Another enzyme makes use of the proton gradient generated by the pump, synthesising adenosine triphosphate (ATP) that powers energy-requiring functions such as muscle contraction and nerve impulses. The central biological importance of this system is evident, for example from the almost immediate death that follows from blocking cell respiration, e.g. by cyanide.

Cytochrome oxidase functions as an energy transducer in much the same way as a fuel cell. It is a biological "nanomachine" that has evolved over billions of years, and has an efficiency better than 90%.

Wikström and his colleagues study both the chemical reaction and the proton pump of cytochrome oxidase by biophysical techniques with a time resolution less than one microsecond. In this way it has been possible to monitor the enzyme’s functions in real time. It takes about one millisecond for the respiratory enzyme to reduce one oxygen molecule to water. This time includes all the partial reactions, and also the efficient energy-transducing mechanism.

The research was supported by grants from the Sigrid Juse´lius Foundation, Biocentrum Helsinki and the Academy of Finland.

Mårten Wikström | alfa
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