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O
O
O
-
O
-
O
O
N
N
N
N
HOCl
O
O
SH
S
Cl
H
2
N
Glutathione
O
-
O
-
H
2
N
O
O
Glutathione sulfenyl
chloride
O
O
-
O
N
N
O
O
S
Glutathione
sulfonamide
O
H
O
-
O
Figure 3.7.
Chlorination of dipeptide (adapted from Armesto et al. [27] with the per-
mission of the Royal Society of Chemistry).
product while gSSg and protein-mixed disulfides were determined only in
minimal quantities. In the proposed mechanism, the formation of glutathione
sulfonamide occurs through a sulfenyl chloride intermediate (Fig. 3.7) [54, 59].
The intramolecular condensation between an intermediate of the Cys side
chain and the amino group of the glutamyl side chain was proposed to result
in glutathione sulfonamide. This sulfonamide may be a specific marker of
HOCl treatment in the biological system.
The oxidation of dipeptides by HOCl occurs through a chlorine atom trans-
fer from the oxygen of HOCl to the terminal amino residue of the peptide
(Fig. 3.8). Water molecules directly participate at the transition state. Participa-
tion of three water molecules in the oxidation of ammonia by HOCl has been
theoretically suggested [62]. The cyclic structure of the transition state permits
the synchronous transfer of Cl and H atoms to proceed without the formation
of charged species and the reducing charge development on the reaction
centers [27]. The determined activation parameters are consistent with the
scheme given in Figure 3.8.
The second-order rate constants provided in Table 3.1 have been utilized
in computational modeling of the reactions of free amino acids in plasma,
apolipoprotein-Al, and human serum albumin (HSA) [28]. The model was
successful in predicting which sites the majority of HOCl reacts with at differ-
ent molar ratios of protein to HOCl. For example, at a low molar ratio of <4 : 1
of HOCl to HSA, the majority of HOCl is consumed by Cys and Met residues.
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