This proposal is to study the local molecular interactions in cytochrome c oxidase from beef heart that control reduction of dioxygen to water and the conservation of chemical energy for sythesis of adenosine triphosphate. These studies will include freeze-trapping of intermediate species at temperatures between 10K and 280K as required. The chemical nature of stable or freeze-trapped cytochrome oxidase derivatives will be characterized by U.V. visible, and near infrared spectra, electron paramagnetic resonance spectra, and by vibrational spectra of ligand complexes with a3Fe and CuB. Fourier transform infrared spectroscopy has provided new information about the reduced oxidase in studies of the carbon monoxide complexes, a3FeCO in the dark, and CuBCO that results from photolysis at low temperature. This has opened new ways to measure structural interactions that control electron flow and oxygen reduction with minimum release of intermediates such as superoxide or peroxide. Pathological states that interfere with this control may cause altered forms that we observe by FTIR spectroscopy of the CO complexes of a3Fe or CuB. Conditions that affect the relative amount of these states will be explored. These studies apply areas of physics, spectroscopy, transition metal chemistry, and computer analysis of band shapes and reaction kinetics to problems of heart physiology and heart disease. The technology that is being developed in the conduct of these experiments will open yet new windows in our study of the heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL028144-04
Application #
3339538
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1982-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210