nic reserves) and fed to active working muscles.
As a result, some of these organs or tissues may
experience transient hypoxia. In addition, during
exercise at or above V
.
o2max., and perhaps at
lower intensities, fibres within the working
muscle may experience hypoxia. During the
exercise recovery phase, these tissues, that were
subject to transient hypoxia during exercise, are
reoxygenated, resulting in the well-known burst
of ROS production that is characteristic of
ischaemia-reperfusion (Kellogg & Fridovich
1975; Wolbarsht & Fridovich 1989).
Catecholamine auto-oxidation
During exercise, catecholamine levels in the cir-
culation may increase severalfold (Singh 1992).
Auto-oxidation of these catecholamines may
represent a significant source of ROS during
exercise.
Xanthine oxidase activity
Mainly located in the vessel walls of most tissues,
including cardiac and skeletal muscle, the
enzyme xanthine dehydrogenase (XDH) cataly-
ses the oxidation of hypoxanthine to xanthine,
and xanthine to uric acid. While in its native
form, XDH uses NAD+as an electron acceptor.
Under certain conditions, e.g. ischaemia–
reperfusion and extreme hypotension as in
haemorrhagic shock, XDH may either reversibly
or irreversibly be transformed to xanthine
oxidase. In contrast to the native dehydrogenase
form, xanthine oxidase utilizes O 2 as the electron
acceptor and produces superoxides as a result
while catalysing the oxidation of hypoxanthine
to uric acid (Hellsten 1994).
Neutrophil oxidative burst
As weapons for pathogen destruction and
immunoprotection, ROS have been put to good
use by phagocytes. Nicotinamide adenine dinu-
cleotide phosphate (NADPH) oxidase located in
the plasma membrane of neutrophils produces
superoxides on purpose. Following spontaneous
294 nutrition and exercise
dismutation, superoxides generated in this way
contribute to H 2 O 2 formation. When activated by
immune-challenge or such other stimuli, neu-
trophils release myeloperoxidase into the extra-
cellular medium. Myeloperoxidase, released as
such, complexes with H 2 O 2 to form an
enzyme–substrate complex with an oxidizing
potential. The complex oxidizes chloride (Cl–) to
produce hypochlorous acid (HOCl). O 2 •–, H 2 O 2
and HOCl may be considered as broad spectrum
physiological ‘antibiotics’ that eliminate patho-
genic infection. Unfortunately, for this, the host
cell has to pay a price in the form of inflammation
(Edmonds & Blake 1994). Oxidative burst in
leucocytes marginated to skeletal muscle during
exercise may cause tissue damage (Weiss 1989;
Ward 1991).Nitric oxide synthesis
Nitric oxide (NO) has one unpaired electron and
is therefore a radical by definition. Cells like
macrophages which are capable of producing
both NO and superoxides are the likely host of a
powerful ROS, the peroxynitrite anion (ONOO–).
Formed by the reaction of NO with superoxide,
the peroxynitrite anion is a relatively long-lived
ROS. In this way, NO may magnify superoxide
toxicity. Human skeletal muscle expresses two
different constitutive isoforms of NO synthase in
different cellular compartments (Frandsen et al.
1996). Activity of skeletal muscle is known to be
associated with a marked increase of NO produc-
tion and release by the tissue (Balon & Nadler
1994). Increased end product of NO metabolism
has been observed in the postexercise plasma of
both athletes and non-athletes (Jungersten et al.
1997).Metal ions
Conditions, e.g. lowering of plasma pH to less
than 6.0, haemolysis, ischaemia-reperfusion, that
lead to the release of transition metal ions, e.g.
iron and copper, may amplify ROS toxicity
(Jenkins & Halliwell 1994).
Other conditions that may contribute to oxida-