Chemistry Reference
In-Depth Information
cromolar (Epsztejn et al. 1997). There is an ongoing debate as to whether only
iron or also copper are involved in H
2
O
2
-induced DNA damage (Barbouti et al.
2001; Bar-Or and Winkler 2002; Galaris et al. 2002). The much higher steady-
state level of damaged DNA bases in mitochondrial DNA as compared to nuclear
DNA has been, at least in part, attributed to the relatively high levels of iron in
mitochondria (Eaton and Qian 2002). It has been noted that supplementation of
iron generates
•
OH in vivo (Kadiiska et al. 1995). Other transition metal ions,
e.g., nickel, cobalt, and chromium, may cause DNA damage (Nackerdien et al.
1991; Datta et al. 1993, 1994; Kasprzak 1996, 1997, 2002; Bal et al. 1997; Kasprzak
et al. 1997). In aqueous solution, lipid hydroperoxides induce DNA strand breaks
(besides base damage) that are considered to be mediated by adventitious DNA-
bound transition metal ions (Yang and Schaich 1996). The nature of the hydro-
peroxide seems to play a mayor role including in the site-specificity (Inouye
1984; Ueda et al. 1985). Iron seems to play a major role in lipid autoxidation
(Minotti and Aust 1989) and DNA damage occurs as a side reaction upon their
elimination with the iron-containing peroxidases (Adam et al. 2000a). Thus, the
chemistry of transition-metal ions with H
2
O
2
and other hydroperoxides will be
discussed in the following. It has been suggested, that in cellular systems “reduc-
tive stress” may reduce these transition-metal ions to their more reactive lower
oxidation states and thus induce a situation commonly connected with “oxida-
tive stress” (Ghyczy and Boros 2001). For all these considerations, it would be of
importance to know the H
2
O
2
concentration in cells. According to a review on
the concentration of H
2
O
2
in the human body (Halliwell et al. 2002), this seems
be still an open question.
2.5.1
Iron
It has been observed by Fenton that Fe
2+
and H
2
O
2
yields a product with a much
higher oxidation power that H
2
O
2
itself [Fenton and Jackson (1899); for a histori-
cal review see Koppenol (1993); for general reviews see Goldstein et al. (1993); Sy-
chev and Isak (1995); Wardman and Candeias (1996)]. This and related reactions
are called Fenton or Fenton-type reactions. With amusement, we noticed that
Schönbein (1857) made use of this reaction even earlier. In two exciting studies,
Haber and Weiss have shown that this strong oxidizing property is due to the
formation of a very short-lived entity which they have attributed to
•
OH [reac-
tion (75)] (Haber and Weiss 1932, 1934).
Fe
2+
+ H
2
O
2
Fe
3+
+
•
OH + OH
−
→
(75)
There is a continuing discussion, whether also (or exclusively) iron in a higher
oxidation state [ferryl; Fe(IV)] is formed [reaction (76)] (Sawyer et al. 1996; Kre-
mer 1999, 2000), but there is increasing evidence [for replies on the paper by
Sawyer et al. (1996) see McFaul et al. (1998) and Walling (1998)] that the concept
of a free
•
OH being formed in this reaction can explain all the observed reactions
and their kinetics, at least with aqua
Fe
2+
in aqueous solution.
−
Search WWH ::
Custom Search