Page 111 - 79_04

Reduction
in
mitochondrial
membrane
peroxidizability
index…

level
of
CEL
and
CML,
was
increased
in
the
heart
after
atenolol
treatment.
These

results
are
in
agreement
with
previous
experiments
in
mice
where
increases
in

CEL
and
CML
were
also
observed
(38).
Several
studies
have
reported
dissociation

between
markers
of
lipoxidation
and
those
of
glycoxidation
or
pure
oxidation.

Thus,
increasing
fatty
acid
unsaturation
in
the
rat
heart
by
dietary
manipulation

strongly
elevated
MDAL,
whereas
CML
(which
can
be
formed
by
lipoxidation
and

glycoxidation)
was
only
slightly
elevated
(52).
On
the
other
hand,
MDAL
negatively

correlated
with
longevity
in
the
heart
of
mammals
(26),
but
no
correlation

between
longevity
and
heart
CML
or
CEL
levels
was
observed
in
the
same

investigation.
Our
results
do
not
clarify
why
CML
and
CEL
were
increased.
The

formation
of
those
protein
adducts
could
involve
chemical
reaction
with
oxidized

fragments
coming
from
carbohydrates
like
glucose,
but
they
may
also
be
formed
at

a
high
rate
from
glycolytic
intermediates
(40).
It
is
possible
that
the
atenolol

treatment
increased
the
concentration
of
glycolytic
intermediates,
and
that
could

explain
why
the
glycoxidation
markers
were
increased
in
our
experiment.

Polyunsaturated
fatty
acids
are
generally
synthesized
by
modification
of

saturated
fatty
acid
precursors
that
are
products
of
fatty
acid
synthase.
This

process
is
catalized
by
two
kind
of
specific
enzymes:
desaturases
and
elongases.

The
enzymatic
steps
of
microsomal
fatty
acid
elongation
involve
the
addition
of

two-­-carbon
units
to
a
fatty
acyl-­-CoA
employing
malonyl-­-CoA
as
the
donor
and

NADPH
as
the
reducing
agent.
To
date,
seven
ELOVL
proteins
(elongase
enzymes

referred
to
as
Elongation
of
very-­-long-­-chain
fatty
acids)
have
been
identified,
with

ELOVL1,
3,
6
and
7
preferring
saturated
and
monounsaturated
fatty
acids
as

substrate
and
ELOVL2,
4
and
5
being
selective
for
polyunsaturated
fatty
acids

(PUFAs).
All
ELOVL
proteins
contain
several
stretches
of
amino
acids
that
are
fully

conserved
in
mice,
rats
and
humans
(53).
The
desaturase
enzymes,
which
are
also

highly
conserved,
insert
double
bonds
at
specific
carbon
atoms
(the
?
number

indicates
the
position
at
which
the
double
bond
is
introduced)
in
the
fatty
acid

chain
and
the
fatty
acid
elongation
system
elongates
the
precursors
in
two-­-carbon

increments
(54).
The
fatty
acid
desaturation
pathway
and
the
deacylation-­-
reacylation
cycle
are
the
main
mechanisms
responsible
for
the
fatty
acid

composition
of
cell
membranes.

In
the
present
investigation
we
estimated
the
desaturase
and
elongase

activities.
The
?5
(n-­-6)
activity
was
lower
in
the
atenolol
group
,
as
it
has
also
been

reported
in
long-­-lived
species,
which
show
several
fold
lower
?5
and
?6

desaturase
activities
than
short-­-lived
ones
(16,55).
This
can
explain
why
22:6n-­-3

and
20:4n-­-6
decrease,
and
18:2n-­-6
and
18:3n-­-3
increase
from
short
to
long-­-lived

animals,
since
desaturases
are
the
rate-­-limiting
enzymes
of
the
n-­-3
and
n-­-6

pathways
synthesizing
the
highly
unsaturated
PUFAs
20:4n-­-6
and
22:6n-­-3
from

their
dietary
precursors,
18:2n-­-6
and
18:3n-­-3,
respectively.
In
our
study
the
global

627