REACTIVE OXYGEN SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 150

TABLE 4.8. Second-Order Rate Constants (/M/s) for the Reactions of Prx's with
Various Hydroperoxides
Hydroperoxide Prx2 Prx3

Lysozyme hydroperoxide 40 90

BSA hydroperoxide 160 360

Histidine hydroperoxide 2 × 10 3 3 × 10 3

N -Acetyl leucine hydroperoxide 4 × 10 4 ND

ND, not determined.
Adapted from Peskin et al. [198] with the permission of the Biochemical Society.

hydroperoxide to 4 × 10 4 /M/s for N -acetyl leucine hydroperoxide. Tyrosine
and gly-Tyr-gly hydroperoxides were slightly slower than the rate with N -
acetyl leucine hydroperoxide, which suggests hydroperoxide on the α-carbon
reacted slowly than those on the side chain. The rate constants provided in
Table 4.8 are within close proximity to the measured values for the reactions
of amino acids for small alkyl hydroperoxides [199]. However, Prx2 and Prx3
had much higher reactivity with H 2 O 2 ( k > 10 7 /M/s) than their reactions with
amino acid hydroperoxides [200, 201]. The reactivity of protein hydroperox-
ides was much slower with rate constants in the range of 4 × 10 1 /M/s to
3.6 × 10 2 /M/s (Table 4.8). Hydroperoxides of Leu and Ile as free amino acids
and in peptides with either or both c- and N-termini blocked reacted rapidly
with Prx2 and Prx3 (Table 4.9). complete oxidation of Prx, except leucine
hydroperoxide, was observed within 10-15 seconds. A significant Prx oxidation
by histidine hydroperoxide was obtained, though the reaction was slow (Table
4.9). The results of Table 4.9 are supported by the rate studies [198]. Rate
constants in the studies suggest that Prx2 and Prx3 may be able to remove
peptide hydroperoxides with half-lives of 1-10 seconds, while a few minutes
would be required to remove protein hydroperoxides [198]. Prx's would thus
be able to prevent the accumulation of intracellularly generated such reactive
hydroperoxides. Secondary damages to other targets by hydroperoxides may
be prevented. The oxidation of Prx by hydroperoxides produced disulfides and
alcohols (Eq. 4.40). The formation of alcohol was confirmed using mass analy-
sis [198]:

2PrxSH ROOH PrxS-SPrx ROH + → + . (4.40)

The reactivity of hydroperoxides of amino acids (Tyr and Trp), peptides
( N -Ac-Trp-Me and gly-Tyr-gly), and bovine serum albumin (BSA) with 26S
proteasome has been examined to understand if oxidized proteins modulate
26S proteasome activity [189]. Impairment of proteasome has been reported
in Alzheimer's and Parkinson's diseases. Results showed that studied hydro-
peroxides modified the activity of 26S proteasome activity. Hydroperoxides of