Chemistry Reference
In-Depth Information
TABLE 4.6. Rate Constants for Reactions of
1
O
2
with Protein Side Chains
Side chain
pH
k
(/M/s)
Reference
cys
7
0.9 × 10
7
[161]
Met
7
1.6 × 10
7
[161]
8.5
2.2 × 10
7
[164]
Tyr
7
0.8 × 10
7
[161]
0.9 × 10
7
8.5
[164]
Trp
7
3 × 10
7
a
[161]
7
2-7 × 10
7
b
[161]
7.5
3.2 × 10
8
a
[160]
8.5
1.8 × 10
8
[164]
His
>8
1.0 × 10
8
[159]
Low pH
0.5 × 10
7
[159]
7.7 × 10
7
c
7.5
[160]
8.5
6.6 × 10
7
[164]
carnosine
7.5
1.3 × 10
8
c
[160]
a
chemical reactions.
b
Physical quenching.
c
Eu
3+
-luminescence probe.
free amino acids have been studied to learn if proteins as cellular components/
sites could be important targets of
1
O
2
[151, 159, 161, 162]. cys, Met, Tyr, Trp,
and His were the only amino acids showing significant reactivity with
1
O
2
at
physiological pH (Table 4.6) [159-161, 163, 164]. Other aliphatic and aromatic
amino acids had much lower reactivity (
k
< 0.7 × 10
7
/M/s). The predicted con-
sumption of
1
O
2
by intracellular targets based on rate constants of the reac-
tions and the average concentration of each component in a typical leukocyte
cell was ∼68% [130]. Other factors such as the limited diffusion radius of
1
O
2
from its site of generation and yields of
1
O
2
would also determine proteins as
potential target of
1
O
2
in a cell.
The pH dependence for the quenching of
1
O
2
by His and Trp is shown in
Figure 4.9 [159]. Histidine had a pronounced effect of pH on the second-order
rate constant, while Trp did not show significant variation of rate. The results
for the rate constants of His were fitted nicely using a p
K
a
of 5.9, suggesting
the protonation state of the imidazole ring in histidine governed the variation
of rates with pH. The lower and upper limits of the rate constants were calcu-
lated as ≤10
4
and 5.0 × 10
7
/M/s, respectively. The unprotonated form of Arg
and Lys also reacted rapidly with
1
O
2
at higher pH values [162]. The lack of
ionizable protons in the indole nucleus of Trp explained the trend in rates with
pH. The ability of
1
O
2
to damage critical targets in a cellular environment thus
depends on the concentration of potential quencher species at a particular
cellular location, which vary with pH.
Several studies have been performed to learn changes in proteins caused
by
1
O
2
-mediated oxidation [13, 130, 134, 160, 163, 165-169]. The interaction of
Search WWH ::
Custom Search