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Protein oxidation by the cytochrome P450 mixed-function oxidation system.
Earl R Stadtman1, Hirofumi Arai, Barbara S Berlett
1Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012, USA. erstadtman@nih.gov
Biochemical and Biophysical Research Communications
|September 6, 2005
Summary
This study explores protein and low-density lipoprotein (LDL) oxidation by mixed-function oxidation (MFO) systems. Results suggest bicarbonate/CO2 buffer systems enhance LDL oxidation more than phosphate buffers, potentially involving bicarbonate derivatives.
Area of Science:
- Biochemistry
- Oxidative Stress Research
Background:
- Oxidation of proteins and low-density lipoprotein (LDL) is implicated in various pathologies.
- Mixed-function oxidation (MFO) systems are crucial for understanding cellular oxidative processes.
Purpose of the Study:
- To review and summarize findings on protein and LDL oxidation by different MFO systems.
- To investigate the role of buffer systems in MFO-mediated LDL oxidation.
Main Methods:
- Review of studies employing various MFO systems (e.g., O2/FeCl3/H2O2/ascorbate, O2/cytochrome P450 reductase/NADPH/FeCl3).
- Comparison of LDL oxidation rates in bicarbonate/CO2 buffer versus phosphate buffer.
- Assessment of component dependency in MFO systems, including substitutions for FeCl3.
Main Results:
- LDL oxidation by O2/FeCl3/H2O2/ascorbate was significantly enhanced by bicarbonate/CO2 buffer compared to phosphate buffer.
- FeCl3 in the O2/FeCl3/H2O2/ascorbate system could be substituted by hemin, hemoglobin, or cytochrome c.
- LDL oxidation by O2/cytochrome P450 reductase/NADPH/FeCl3 showed only a slight increase (25%) in bicarbonate/CO2 buffer and was independent of FeCl3, with omission causing a 60% activity loss.
Conclusions:
- Bicarbonate/CO2 buffer systems appear to play a significant role in promoting LDL oxidation via certain MFO systems.
- Peroxymonocarbonate and/or free radical derivatives of bicarbonate/CO2 may contribute to LDL oxidation in these MFO systems.