Biomedical Engineering Reference
In-Depth Information
major contributor to the
Pi
ATP
reaction flux measured by
the
31
P MT approaches in E. coli
(118)
, yeast
(119)
, liver
(120)
,
and the myocardium
(121)
. For instant, in the perfused rat heart,
GAPDH/PGK mediated exchange dominates the
Pi
→
ATP
flux
measured by the
31
P MT approach in the myocardium
(121)
.
Under these circumstances,
only if
the GAPDH/PGK effect
was eliminated either directly using exogenous inhibitor iodoac-
etate or indirectly by eliminating all exogenous and endogenous
sources of glucose, the myocardium
Pi
→
ATP
flux determined
by the in vivo
31
P MRS MT measurement was found to be the
same as the net rate of
oxidative
ATP synthesis calculated as the
product of the cardiac oxygen consumption rate and the P:O
ratio, and then the correlation between the measured flux and
oxygen consumption rate became evident
(121)
. These obser-
vations and findings reveal the complexity of biological systems
and potential limitation of in vivo
31
P MRS MT approaches for
directly measuring the ATP metabolic flux related to oxidative
phosphorylation in some organs such as heart and liver. Inter-
estingly, in contrast to the observations in the myocardium, and
analogous observations in yeast, E. coli and liver, the
Pi
→
ATP
flux measured by in vivo
31
P MRS MT in the human brain is simi-
lar to the net oxidative ATP synthesis rate which can be estimated
by the available CMRO
2
data and the P:O ratio based on a tight
link between the cerebral oxidative phosphorylation and oxygen
utilization under normal physiological condition
(20, 50)
.The
CMRO
2
value in the human occipital lobe has been measured
to be 1.71
→
mol/g/min by PET
(91)
. The ATP synthesis rate
attributed by oxidative phosphorylation can be calculated by mul-
tiplying this CMRO
2
value by the P:O ratio of
μ
∼
2.5
(122)
and
μ
factor of 2, resulting in an estimated value of 8.6
mol/g/min.
This rate is almost identical to the cerebral ATP synthesis rate of
F
ATP
ase
f
mol/g/min, which was directly measured by in
vivo
31
PMRSMT
(50)
. A similar relation was also evident in
the animal studies showing a tight correlation between the mea-
sured
Pi
=8.8
μ
ATP
flux and the estimated oxidative phosphor rate
(49, 123)
. These comparisons of results, thus, lead us to conclude
that in the brain, the Pi
→
ATP flux measured by the in vivo
31
P
MT approach equals the net oxidative ATP synthesis rate linking
to the cerebral oxidative phosphorylation, and this flux should
provide a vital index reflecting the major bioenergetics for sup-
porting brain activity and function
(7, 12, 20, 123)
. This conclu-
sion makes in vivo
31
P MT attractive for studying the central role
of the cerebral bioenergetics associated with oxidative phospho-
rylation and brain activity, though the underlying mechanism for
explaining the discrepancy in the
31
P MT measurements between
the brain and other organs (e.g., heart and liver) remains to be
explored
(20)
.
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