HALOGENATED SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 94

Val-gly. Aldehydes as products of the reactions were observed. The suggested
mechanism involves oxidative deamination and decarboxylation to form cor-
responding aldehydes [108-110].
3.2.2 Halogen Transfer by Halamines
The second-order rate constant determined for chlorine transfer reactions of
NH 2 Cl with amino acids are summarized in Table 3.4 [29, 60, 111-113]. The
rate constants were about five orders of magnitude smaller than the corre-
sponding constants for HOCl (see Table 3.1). Only a limited number of rate
constants for NH 2 Br are available (Table 3.4). The rate constants for the reac-
tions with Met and gSH with NH 2 Br were much faster than those with NH 2 Cl.
Based on the reaction of halamines with gSH, NH 2 Br was suggested to be
more selective than NH 2 Cl [114]. This selectivity was also observed in the
reaction of NH 2 Br with ascorbic acid, which was 60 times faster than the cor-
responding reaction of NH 2 Cl [28, 64].
Reactions of chloramines, formed on the biological molecules, with possible
targets of proteins have been studied [60, 111, 114-118]. The chloramines
formed on the imidazole groups of His and nucleobases (thymidine mono-
phosphate [TMP], guanosine monophosphate [gMP], and inosine) were
usually more reactive than the chloramines formed on primary amines [119].
The second-order rate constants of chloramines on amino acids and small
peptides with amines and thiols are summarized in Table 3.4. Rate constants
for gly, His, gly, and N -α-acetyl-lys chloramines with Met, Cys, and gSH
were more than five orders of magnitude lower than for the corresponding
reactions of HOCl (see Table 3.1). The rate constants of taurine chloramine
with thiols varied from 3.9 × 10 1 /M/s to 5.6 × 10 2 /M/s. Significantly, these rate
constants had a strong inverse relationship with the p K a values of thiols [60].
Chloramines of gly and N -α-acetyl-lys also had a similar relationship, but
their rate constants were higher than for chloramines of Tau. The reactivity of
His chloramines with Cys and N -Ac-Cys was higher than those of gly, taurine,
or N -α-acetyl-lys chloramines (Table 3.4). The general trend of the reactivity
of these chloramines species was histamine > N -acetyl-lys > gly > taurine.
An increase in negative charge in the vicinity of chloramines decreased the
rate. As expected, neutral Met thioether did not show such dependence on
charge; therefore, the order of decreasing reactivity was gly > histamine > N -
α-acetyl-lys > taurine (Table 3.4). The kinetics results summarized in Table
3.4 suggest the possible oxidation of thiols by chloramines in vivo may cause
selective inactivation of the enzyme. For example, the chloramine of Tau was
more effective than HOCl at inhibiting the thiol-dependent enzymes, creatine
kinase and gAPDH [120].
The rate constants for the oxidation of gSH and peroxiredoxin 2 (Prx2) by
HOCl, NH 2 Cl, and gly-Cl have been determined (Tables 3.1 and 3.4) [29, 60,
111-113]. gSH was about five times more reactive with NH 2 Cl than gly-Cl,
but the reactivity of Prx2 was at least three orders of magnitude greater for