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284 Tissues and organs

Erythrocyte metabolism antioxidants include vitamins C and E (see
pp. 364, 368), coenzyme Q (see p. 104), and
Cells living in aerobic conditions are depen- several carotenoids (see pp. 132, 364). Biliru-
dent on molecular oxygen for energy produc- bin, which is formed during heme degrada-
tion. On the other hand, O 2 constantly gives tion (see p. 194), also serves for protection
rise to small quantities of toxic substances against oxidation.
known as reactive oxygen species (ROS). Glutathione, a tripeptide that occurs in
These substances are powerful oxidation high concentrations in almost all cells, is par-
agents or extremely reactive free radicals ticularly important. Glutathione (sequence:
(see p. 32), which damage cellular structures Glu–Cys–Gly) contains an atypical γ-peptide
and functional molecules. Due to their role in bond between Glu and Cys. The thiol group of
O 2 transport, the erythrocytes are constantly the cysteine residue is redox-active. Two mol-
exposed to high concentrations of O 2 and are ecules of the reduced form (GSH, top) are
therefore particularly at risk from ROS. bound to the disulfide (GSSG, bottom) during
oxidation.
A. Reactive oxygen species
C. Erythrocyte metabolism
Thedioxygen molecule(O 2 )contains two un-
paired electrons—i. e., it is a diradical. Despite Erythrocytes also have systems that can in-
this, O 2 is relatively stable due to its special activate ROS (superoxide dismutase, catalase,
electron arrangement. However, if the mole- GSH). They are also able to repair damage
cule takes up an extra electron (a), the highly caused by ROS. This requires products that
–
reactive superoxide radical ( O 2 ) arises. An- are supplied by the erythrocytes’ mainte-
other reduction step (b)leads to the peroxide nance metabolism, which basically only in-
2–
anion (O 2 ), which easily binds protons and volves anaerobic glycolysis (see p. 150) and
thus becomes hydrogen peroxide (H 2 O 2 ). In- the pentose phosphate pathway (PPP; see
clusion of a third electron (c)leads to cleavage p. 152).
–
of the molecule into the ions O 2– and O . The ATP formed during glycolysis serves
+
+
While O 2– can form water by taking up two mainly to supply Na /K -ATPase, which main-
–
protons, protonation of O provides the ex- tains the erythrocytes’ membrane potential.
tremely dangerous hydroxy radical ( OH). A The allosteric effector 2,3-BPG (see p. 282) is
fourth electron transfer and subsequent pro- also derived from glycolysis. The PPP supplies
+
–
tonation also convert O into water. NADPH+H , which is needed to regenerate
The synthesis of ROS can be catalyzed by glutathione (GSH) from GSSG with the help
iron ions, for example. Reaction of O 2 with of glutathione reductase [3]. GSH, the most
FMN or FAD (see p. 32) also constantly pro- important antioxidant in the erythrocytes,
duces ROS. By contrast, reduction of O 2 by serves as a coenzyme for glutathione peroxi-
cytochrome c-oxidase (see p. 140) is “clean,” dase [5]. This selenium-containing enzyme
as theenzymedoes not releasethe intermedi- detoxifies H 2 O 2 and hydroperoxides, which
ates. In addition to antioxidants (B), enzymes arise during the reaction of ROS with unsatu-
also provide protection against ROS: superox- rated fatty acids in the erythrocyte mem-
ide dismutase [1] breaks down (“dispropor- brane. The reduction of methemoglobin
3+
2+
tionates”) two superoxide molecules into O 2 (Hb Fe )to Hb (Hb Fe ,[4]) is carried out
and the less damaging H 2 O 2 . The latter is in by GSH or ascorbate by a non-enzymatic
turn disproportionated into O 2 and H 2 Oby pathway; however, there are also NAD(P)H-
heme-containing catalase [2]. dependent Met-Hb reductases.

B. Biological antioxidants

To protect them against ROS and other radi-
cals, all cells contain antioxidants.These are
reducing agents that react easily with oxida-
tive substances and thus protect more impor-
tant molecules from oxidation. Biological

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