REACTIVE SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 20

1.3 REACTIVE SPECIES
Amino acids play many roles in the metabolic activities of humans [192]. For
example, amino acids are involved in the efficiency of utilizing dietary proteins,
the cell-specific metabolism of nutrients, cell signaling, and oxidative stress
[193, 194]. Reactive intermediates produced in the body influence metabolic
activities by altering side chains of amino acids and modifying protein back-
bones (polypeptide chains) [195]. This section summarizes the involvement of
reactive intermediates in biological systems. The generation and reactivity of
the intermediates are described in Chapters 3-6.
1.3.1 Halogen Species
The heme enzyme myeloperoxidase (MPO) is linked to atherosclerosis [196].
Reactions between halide/pseudohalide (Cl − , Br − , and SCN − ) ions and hydro-
gen peroxide (H 2 O 2 ) are catalyzed by MPO to produce HOCl, HOBr, and
hypothiocyanous acid (HOSCN) [197]. The concentrations of Cl − , Br − , and
SCN − in plasma are in the ranges of 100-140 mM; 20-100 μM, and 20-250 μM,
respectively. HOCl and HOBr are powerful oxidants and react at multiple
targets (Chapter 3) [198]. These oxidants can cause tissue damage at excessive
levels. HOCl and HOBr have been implicated in kidney disease, inflammatory
bowel disease, cardiovascular disease, asthma, cystic fibrosis, rheumatoid
arthritis, and neurodegenerative conditions [199, 200]. SCN − reacts much faster
with H 2 O 2 (730-fold) than with Cl − ; hence, most of H 2 O 2 is transferred into
HOSCN. A high level of HOSCN has been observed in smokers due to their
elevated levels of SCN − [197]. HOSCN is less reactive compared to HOCl
and HOBr, but is highly selective. Reactions of HOSCN are predominately
with thiols (e.g., GSH) (Chapter 3). The ratio of [GSH]/[oxidized glutathione
(GSSG)] may be useful to detect early atherosclerosis [201]. Overall, the con-
centration of SCN − determines the damage induced by MPO. The chemistry
of HOCl, HOBr, and HOSCN and their oxidation of amino acids including
thiols are discussed in Chapter 3. Halamines (e.g., RNHCl and RHBr) can be
produced as intermediates in reactions of HOCl and HOBr and may partici-
pate in reactions of biological systems. Hydrolysis, halogen transfer, and reduc-
tion of halamines are presented in Chapter 3.
Chlorine dioxide (ClO 2 ) is an important biocide and bleach [202]. Genera-
tion of ClO 2 using different methods including that from chlorite ion at
neutral pH under mild conditions in the presence of water-soluble, manganese
porphyrins and porphyrazines [203] is discussed in Chapter 3. Mechanisms
of decomposition of ClO 2 under neutral and alkaline conditions are also
given in Chapter 3. Finally, oxidation of inorganic and organic compounds
(e.g., amino acids, peptides, and proteins) by ClO 2 is summarized in
Chapter 3.