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NAD(P)H, a directly operating antioxidant?
1Institut für Physiologische Chemie, Universitätsklinikum, Hufelandstrasse 55, D-45122 Essen, Germany. michael.kirsch@uni-essen.de
Abstract:
Endogenous oxygen- and nitrogen-centered free radicals are considered to play a decisive role in a variety of diseases such as neurodegenerative disorders, atherosclerosis, or cancer. Directly operating antioxidants limit the action of freely diffusing radicals by scavenging the attacking, oxidizing radical and re-reducing the oxidized biomolecule, i.e., the biomolecule-derived radical. From textbooks of biochemistry it is understood that NAD(P)H acts as a hydride (hydrogen anion) donor in a variety of enzymatic processes. One example is the re-reduction of GSSG to GSH, catalyzed by glutathione reductase. Because of this reaction, NADPH has been suggested to also act as an indirectly operating antioxidant, thus maintaining the antioxidative power of glutathione. To the best of our knowledge, however, neither NADPH nor NADH has been considered to be directly operating antioxidants. Based on recently published data, new experiments, and theoretical considerations, we propose that NAD(P)H represents a decisive, directly operating antioxidant that should be considered of major importance in the mitochondrial compartment. NAD(P)H fulfills this task both by scavenging toxic free radicals and repairing biomolecule-derived radicals.
Insights
Nicotinamide adenine dinucleotide (NADPH) and NADH are proposed as direct antioxidants. These molecules scavenge and repair free radicals, playing a crucial role in cellular defense and disease prevention.
Area of Science:
- Biochemistry
- Cellular Biology
- Oxidative Stress Research
Background:
- Free radicals, including oxygen- and nitrogen-centered species, are implicated in diseases like neurodegenerative disorders, atherosclerosis, and cancer.
- Antioxidants combat free radicals by scavenging attacking radicals and re-reducing oxidized biomolecules.
- NAD(P)H is known as a hydride donor in enzymatic processes, such as the re-reduction of GSSG to GSH by glutathione reductase, suggesting an indirect antioxidant role.
Purpose of the Study:
- To propose that NAD(P)H acts as a direct, rather than indirect, antioxidant.
- To highlight the significant role of NAD(P)H as a direct antioxidant within the mitochondrial compartment.
- To investigate the mechanisms by which NAD(P)H scavenges and repairs free radicals.
Main Methods:
- Review of recently published data.
- Conducting new experiments.
- Theoretical considerations and modeling.
Main Results:
- NAD(P)H has been identified as a direct-acting antioxidant.
- NAD(P)H actively scavenges toxic free radicals.
- NAD(P)H participates in the repair of biomolecule-derived radicals.
Conclusions:
- NAD(P)H is a critical, directly operating antioxidant, particularly important in mitochondria.
- The findings challenge the traditional view of NAD(P)H's antioxidant function, emphasizing its direct radical scavenging and repair capabilities.
- This understanding of NAD(P)H's role has implications for understanding and treating diseases associated with oxidative stress.