The study of the metabolism of oxygen by cytochrome oxidase (aa3), a binuclear iron copper redox center as compared with the mononuclear cytochrome Omicron types of oxidases sheds light on the essential sequence reactions in oxygen reduction. In cytochrome (aa3) oxidase the formation of bound peroxides, the rupture of the peroxide bond and the generation of radical intermediates form steps where sequestered and nonsequestered radical intermediates can render the system biologically safe or dangerous, respectively. The optical study of the steps in these radical reactions are complemented by studies of the charge densities of the metal atoms, the nature of the ligand shells and the distance to the nearest and next to nearest ligands in the radical intermediates by the use of X-ray synchrotron radiation to determine the edge and EXAFS (Extended X-Ray Absorption Fine Structure) properties. These studies form the basis for the understanding of normoxic and hyperoxic metabolism of oxygen and are essential to molecular explanations of processes leading to the pathway of fibrotic and interstitial lung disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031909-04
Application #
3343062
Study Section
(SSS)
Project Start
1983-06-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University City Science Center
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Naqui, A; Powers, L; Lundeen, M et al. (1988) On the environment of zinc in beef heart cytochrome c oxidase: an x-ray absorption study. J Biol Chem 263:12342-5
Kumar, C; Naqui, A; Powers, L et al. (1988) Does the peroxide compound of cytochrome oxidase contain a ferryl iron? J Biol Chem 263:7159-63
Chance, B; Waterland, R A; Tanaka, A et al. (1988) Mitochondrial function in normal and genetically altered cells and tissues. Ann N Y Acad Sci 550:360-73
Bunker, G; Petersson, L; Sjoberg, B M et al. (1987) Extended X-ray absorption fine structure studies on the iron-containing subunit of ribonucleotide reductase from Escherichia coli. Biochemistry 26:4708-16
Li, Y; Naqui, A; Frey, T G et al. (1987) A new procedure for the purification of monodisperse highly active cytochrome c oxidase from bovine heart. Biochem J 242:417-23
Lundeen, M; Chance, B; Powers, L (1987) The transmembrane helices of beef heart cytochrome oxidase. Biophys J 51:693-5, 697
Jamieson, D; Chance, B; Cadenas, E et al. (1986) The relation of free radical production to hyperoxia. Annu Rev Physiol 48:703-19
Naqui, A; Chance, B; Cadenas, E (1986) Reactive oxygen intermediates in biochemistry. Annu Rev Biochem 55:137-66
Naqui, A; Chance, B (1986) Enhanced superoxide dismutase activity of pulsed cytochrome oxidase. Biochem Biophys Res Commun 136:433-7
Powers, L; Chance, B (1985) Multiple structures and functions of cytochrome oxidase. J Inorg Biochem 23:207-17

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