Biology Reference
In-Depth Information
Thus
Ph
-2/2HbO is likely to be involved in a redox reaction(s) associ-
ating diatomic ligands and their derived oxidative species. Such a reaction is
not unusual, since globins generally display NO dioxygenase activity leading
to nitrate synthesis (
Fl¨gel, Merx, G¨decke, Decking, & Schrader, 2001;
Gardner et al., 2006
;
Fig. 8.7
B). It is noteworthy that
Ph
-2/2HbO provides
protection against NO and related reactive species (
Fig. 8.7
D), under aero-
bic conditions (
Coppola et al., 2013
; see
Section 6.2.4
). Moreover,
Ph
-2/
2HbO exhibits a twofold higher nitrite-reductase activity than horse Mb
at pH 7.0, 25
C. This evidence suggests (
Fig. 8.7
C) that, during an anaer-
obic phase,
Ph
-2/2HbO may supply NO via nitrite reduction (
Russo
et al., 2013
).
Other reactions (
Fig. 8.7
E) may involve complex ROS chemistry
(
Fl¨gel, G¨decke, Klotz, & Schrader, 2004
). O
2
is necessary for bacterial
metabolism, but can become poisonous if it is responsible for oxidative-stress
burst. A number of reactions take place between ROS and the haem-Fe
atom since O
2
is reduced by four e
before yielding a water molecule with
three ROS intermediates, whereas the haem-Fe atom is susceptible to oxi-
dation from
4. In general, pentacoordinated globins are more prone
to ROS oxidation than hexacoordinated forms (
Herold, Kalinga, Matsui, &
Watanabe, 2004; Lardinois, Tomer, Mason, & Deterding, 2008
). However,
in
Ph
-2/2HbO, due to the low affinity of the haem for distal Tyr (weak pro-
tection) in ferrous and ferric states, the protection against deleterious oxida-
tion at high ROS concentration (autocatalytic oxidations
þ
2to
þ
leading to
irreversible haem oxidation and globin degradation)
is not expected
(
Russo et al., 2013
).
The redox state of
Ph
-2/2HbO
in vivo
will depend on the presence of
specific reductases and on the O
2
levels. The redox state could be involved
in an electron-transfer reaction or in a regulatory mechanism with the pro-
tein acting as a redox sensor. In fact, at high O
2
concentration, in the pres-
ence of a reducing system that can compensate for autoxidation, the globin
will be mainly ferrous, but under intermediate conditions it could be in the
ferric form. This behaviour has been observed in pentacoordinated sperm
whale and pig Mb (II), probably upon nucleophile attack such as that medi-
ated by water (
Brantley, Smerdon, Wilkinson, Singleton, & Olson, 1993
),
and in hexacoordinated bis-His form of the globin GLB-26 of the nematode
worm
Caenorhabditis elegans
and of human Ngb, which promotes O
2
reduc-
tion (
Kiger et al., 2011
). By analogy, the hexacoordinated His-Fe-Tyr
adduct of
Ph
-2/2HbO (
Fig. 8.7
F) may be involved in electron transfer
(
Russo et al., 2013
).
