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.
| Fiamingo, F G; Jung, D W; Alben, J O (1990) Structural perturbation of the a3-CuB site in mitochondrial cytochrome c oxidase by alcohol solvents. Biochemistry 29:4627-33 |
| Moh, P P; Fiamingo, F G; Alben, J O (1987) Conformational sensitivity of beta-93 cysteine SH to ligation of hemoglobin observed by FT-IR spectroscopy. Biochemistry 26:6243-9 |
| Chang, S B; Alben, J O; Wisner, D A et al. (1986) Phospholipids chiral at phosphorus: Fourier-transform infrared study on the gel-liquid crystalline transition of chiral thiophosphatidylcholine. Biochemistry 25:3435-40 |
| Fiamingo, F G; Altschuld, R A; Alben, J O (1986) Alpha and beta forms of cytochrome c oxidase observed in rat heart myocytes by low temperature Fourier transform infrared spectroscopy. J Biol Chem 261:12976-87 |
| Fiamingo, F G; Alben, J O (1985) Structures of photolyzed carboxymyoglobin. Biochemistry 24:7964-70 |
