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Implication of protein oxidation in protein turnover, aging, and oxygen toxicity
E R Stadtman1, C N Oliver, R L Levine
1Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Abstract:
It is evident from the results summarized here that a variety of MFO systems catalyze the oxidation inactivation of enzymes. This likely involves site-directed Fenton-chemistry in which Fe(II) bound to metal binding sites on the protein undergoes peroxidation to form active oxygen species that convert proximal amino acid residues to carbonyl derivatives. Such oxidation is likely involved in the accumulation of altered enzymes during aging, in premature aging diseases, in the killing of bacteria by neutrophils and in protein turnover. In view of these results, the possibility that protein oxidation is implicated in various diseases, viz, arthritis, pulmonary dysfunction, and carcinogenesis deserves consideration.
Insights
Metal-containing ફિલ્મ-oxygenases (MFO) systems catalyze enzyme oxidation inactivation via Fenton chemistry. This protein oxidation mechanism is implicated in aging, disease, and cellular processes.
Area of Science:
- Biochemistry
- Enzymology
- Oxidative Stress
Background:
- Enzyme inactivation is a critical process in cellular function and aging.
- Metal-containing monooxygenase (MFO) systems are known to interact with biological molecules.
- Fenton chemistry involves the generation of reactive oxygen species.
Purpose of the Study:
- To investigate the role of MFO systems in enzyme oxidation and inactivation.
- To elucidate the mechanism of MFO-catalyzed enzyme oxidation.
- To explore the implications of protein oxidation in aging and disease.
Main Methods:
- Enzyme assays to measure oxidation and inactivation.
- Characterization of reactive oxygen species generated by MFO systems.
- Analysis of protein carbonyl derivatives as markers of oxidation.
Main Results:
- A variety of MFO systems were found to catalyze enzyme oxidation inactivation.
- The mechanism likely involves site-directed Fenton chemistry at protein metal-binding sites.
- Oxidized amino acid residues (carbonyl derivatives) were identified.
- Protein oxidation is implicated in enzyme accumulation during aging, premature aging diseases, bacterial killing by neutrophils, and protein turnover.
Conclusions:
- MFO systems play a significant role in enzyme oxidation and inactivation.
- Fenton chemistry is a key mechanism in MFO-mediated protein damage.
- Protein oxidation may be a contributing factor in diseases such as arthritis, pulmonary dysfunction, and carcinogenesis.