NADPH, a directly operating antioxidant

NADPH, a directly operating antioxidant

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 rereducing
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.—Kirsch,
M., de Groot, H. NAD(P)H, a directly operating antioxidant?
FASEB J. 15, 1569–1574 (2001)…

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