REACTIVE SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 7

ROS and RNS over available antioxidant biomolecules that subsequently
induce modification of proteins, peroxidation of lipid, and damage of DNA
resulting in diseases such as cancer, cardiovascular disease, diabetes, and ath-
erosclerosis [35]. The significance of Cu and Fe in AD and PD is described in
the previous subsection. Elevated levels of copper have been detected in
tissues of serum and tumors of cancer patients in comparison to healthy
persons. The ratios of Cu : (Fe, Zn, and Se) have also been detected at higher
levels in cancer patients than in normal subjects [53]. Copper can catalyze the
formation of ROS and also decrease the levels of GSH [54, 55]. Increased
levels of copper could play an important role in the development of various
cancers. The interaction between Cu and homocysteine may be involved in
atherosclerosis [56]. This interaction generates free radicals, which oxidize
low-density lipoprotein (LDL), and oxidized products have been found in
atherosclerosis plaques.
Excess levels of iron can be toxic due to its role in producing hydroxyl
radicals (Fenton reaction, Fig. 1.3), which are involved in oxidizing DNA. More
than 100 oxidized products, both carcinogenic and mutagenic, have been iden-
tified. The most common DNA oxidized product is 8-hydroxyguanine (Fig. 1.3)
[35]. The lipid peroxidation process, involved in coronary artery disease, is
catalyzed by iron [57] (Fig. 1.3). The initial formation of the peroxyl radical
(ROO • ) rearranges into endoperoxides through a cyclization reaction, which
leads to the formation of malondialadehyde (MDA). The other major product
of the lipid peroxidation process is 4-hydroxy-2-nonenal. Reactions between
MDA and DNA bases produce adducts (Fig. 1.3) such as M 1 C, M 1 A, and M 1 G
formed from DNA bases cytosine, adenosine, and guanine, respectively [58].
A significant increase in the levels of 8-OH-G, 2-hydroxy-adenine, and
8-hydroxy-adenine adducts have been detected in rectum and colon biopsies
[59].
Chromium(VI) at high levels is considered to be a risk to human health.
Some compounds of Cr(VI) may cause skin cancer when they come in contact
with skin. Further details on the toxic effects of Cr and related mechanisms
are discussed in Chapter 6. Vitamin B 12 is 4% cobalt by mass, which contributes
to toxic and carcinogenic effects. Cobalt in the presence of O 2 generates Co(I)-
OO • , which, through catalysis by SOD, forms Co(I) and H 2 O 2 [60, 61]. The
reaction between Co(I) and H 2 O 2 results in • OH, which induces damage to
DNA and inhibits DNA repair [62].
The redox inactive metals (Zn, Cd, and Pb) generate toxic effects when
undergoing bond formation with sulfhydryl groups of proteins and depletion
of GSH. The exposure of Pb to adolescents represents a serious health threat
worldwide [63]. The toxic effects of Pb include hypertension, cognitive impair-
ments, and neurological disorders [64, 65]. Both ROS and RNS have been
implicated in hypertension due to their exposure to humans [66]. A number
of studies have shown arsenic is carcinogenic [67]. Adverse health effects of
arsenic from contaminated water include anemia, skin lesions, peripheral