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R
1
R
4
O
R
1
R
4
O
δ
-
δ
+
O
-
N
O
-
OH
-
+
N
HO Cl
N
N
Cl
R
2
R
3
O
R
2
R
3
O
R
1
R
4
O
O
-
N
HOCl +
H
N
H
R
2
R
3
O
O
H
H
R
4
R
1
R
4
O
O
H
R
1
Cl
O
O
-
O
-
N
H
2
O +
+
H
H
N
N
Cl
O
R
2
R
3
O
O
R
2
R
3
H
O
H
H
Figure 3.8.
Mechanism of formation of glutathione sulfonamide following treatment
of gSH with HOCl (adapted from Hawkins et al. [33] with the permission of Springer
America).
However, at a larger molar ratio of 8 : 1 and 17 : 1, consumption of HOCl by
Cys and Met is reduced significantly due to consumption also occurring by
cystine, His, and lys residues. At very high molar ratios of 67 : 1 and 170 : 1,
consumptions of HOCl would be ∼37%, 25%, 25%, and 9% by lys, cystine,
His, and Met residues, respectively. The consumption behavior of HOCl in
reaction with Apo-A having no Cys residue would be different [28]. A mass
analysis of HSA after treatment with HOCl identified five different lys modi-
fication sites (lys-130, lys-257, lys-438, lys-499, and lys-598) [63].
3.1.2 Hypobromite
3.1.2.1 Kinetics of HOBr.
The second-order rate constants for reactions of
amino acids and amides with HOBr are provided in Table 3.2 [64]. The rate
constants for gly, Ala, and Val were on the order of 10
6
/M/s, while their cyclic
compounds had much lower rate constants (
k
∼ 10
2
-10
3
/M/s). The variation in
rate constants for various peptide amines was four orders of magnitude, similar
to that of HOCl [28]. Such variations in rate constants could be attributed to
a combination of charge (neutral vs. charged) and conformational (cyclic vs.
linear) effect [28]. The rate constants of the side-chain sulfur-containing amino
acids with HOBr are limited. A few studies reported the rate constants in the
range of 10
5
-10
7
/M/s (Table 3.2). Overall, the rate constants varied by eight
orders of magnitude and an increase in the order of gln/Asn < backbone
amides < Arg << Tyr ∼ lys < disulfide < α-amino ∼ His ∼ Met ∼ Trp < Cys.
The rate constants for the reactions of amines and amides in amino acids
with HOBr were 5-100 times higher than those for HOCl [9]. However, the
rates for Cys and Met residues with HOBr were slightly slower than with
HOCl. Disulfide bonds reacted similarly with both HOBr and HOCl. The rate
constants for the oxidation of Tyr and Trp side chains with HOBr were 5000
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