Chemistry Reference
In-Depth Information
Selenomethionine
Se
NADP
+
R-OOH
GS-SG
O
R = protein
peptide
amino acid
H
2
N
Glutathione
reductase
OH
O
2 GSH
Se
TrxR
ox
R-OH
O
Trx-(SH)
2
H
2
N
OH
NADPH
Selenomethionine
selenoxide
TrxR
red
Trx-(S)
2
Figure 4.13.
Proposed mechanisms for the enhanced peroxidatic activity detected in
SeMet-supplemented cells exposed to gly-His-gly and
N
-Ac-Trp-OMe hydroperox-
ides (adapted from Rahmanto and Davies [202] with the permission of Elsevier, Inc.).
reducing agent was tested using murine macrophage-like J774A.1 cells (Fig.
4.13). A greater removal of two peptide peroxide hydroperoxides (gly-His-
gly and
N
-Ac-Trp-OMe) was observed in the application of SeMet in these
tests. SeMet may thus be involved in the catalytic activity of removing peptide
hydroperoxides of peptide and proteins [202].
In summary, side chains of cys, Met, cystine, Trp, Tyr, and His are most
likely to be oxidized by
1
O
2
. Rates of modification of proteins by
1
O
2
depend
on other components present in solution. However, determined rates in
in
vitro
studies should be used with caution in predicting intracellular phenom-
ena because proteins tend to change structure and conformation and may also
exist in form different from those
in vitro
experiments [203]. Studies on exam-
ining the influence of protein dynamics on the behavior of
1
O
2
are forthcom-
ing, but work on studying reactions of a wide range of proteins with
1
O
2
should provide understanding the mechanism of
1
O
2
-induced cell death. A
significant progress on identifying
1
O
2
-modiied oxidized products of side
chains of proteins, particularly Trp, has been made; however, much more
research in this area using advanced analytical techniques is needed to fully
characteriz the oxidized products. Furthermore, peroxide species have been
determined to be the key species in protein damages induced by
1
O
2
, but
limted information is currently known on their reactivity with biological mol-
ecules. More studies on protein peroxide and their effects on cellular enzymes
may determine if these species are responsible in disease progression. A gas-
phase approach using chemically generated “clean”
1
O
2
using electrospray
ionization (ESI) and ground-ion-beam scattering methods have been applied
to gain insight on the mechanism of the reactions of protonated cys and Trp
with
1
O
2
[204]. Such experimental studies combined with density functional
Search WWH ::
Custom Search