Biomedical Engineering Reference
In-Depth Information
Oxygen and glucose are the major chemical substrates for brain
metabolism and they are continuously supplied by the circulat-
ing blood in the capillary bed. Glucose is first converted to two
pyruvate molecules in the cytosol, then the pyruvate enters the
mitochondria and is metabolized oxidatively with diffused oxy-
gen molecules through the mitochondrial respiratory chain and
the cytochrome oxidase enzyme resulting in substantial oxygen
utilization and final products of water and CO
2
(i.e., Reaction 1
or
R1
in
Fig. 15.1
). This oxygen metabolism is coupled with
the oxidative phosphorylation for producing ATP from inorganic
phosphate (Pi) and adenosine diphosphate (ADP) through the
enzyme of F
1
F
0
-ATP
ase
inside the mitochondria (i.e., Reaction
2or
R2
in
Fig. 15.1
). In general, the mitochondrial oxidative
phosphorylation dominates up to 90% of ATP production
(11)
.
In contrast, ATP utilization mainly occurs in the cytosol space
resulting in ADP and Pi products (i.e., Reaction 5 or
R5
in
Fig. 15.1
), ultimately, providing chemical energy for supporting
various cellular activities and brain functions, in which a significant
amount of ATP energy is used for neuronal signaling. This ATP
utilization is particularly essential for maintaining and restoring
the Na
+
/K
+
ion gradients across the cellular membranes through
the enzyme of Na
+
/K
+
-ATP
ase
as well as for supporting the sig-
naling process (e.g., neuronal transmission and cycling) at resting
and activated brain states
(11-14)
.
The high energy demand in the brain causes extremely
fast chemical cycling among ATP, ADP and Pi, which requires
rapid transportation of these phosphate components between the
cytosolic and mitochondrial compartments. This energy trans-
portation could be partially accomplished by phosphocreatine
(PCr) through the reversible creatine kinase (CK) reaction, thus,
maintaining a stable ATP level in the brain cells
(15-17)
.There
are at least two apparently coupled CK reactions: one occurring
in the mitochondrial intermembrane space (i.e., Reaction 3 or
R3
in
Fig. 15.1
) and another one occurring in the cytosol space
(i.e., Reaction 4 or
R4
in
Fig. 15.1
) although, in reality, these
coupled CK reactions likely exist of these subcellular spaces. They
play an important role in carrying the ATP molecules generated
in the mitochondria into the cytosol for energy utilization, and
then to bring the products of ADP and Pi back to mitochondria
for sustaining ATP production. Therefore, PCr serves a vital role
for energy transportation among subcellular compartments. Four
ATP-related reactions (two reactions each for ATP
ase
and CK)
constitute a complex ATP metabolic process. They are tightly
coupled and integrated with the oxygen metabolism and the
hemodynamic process as depicted in
Figure 15.1
for controlling
the dynamics of ATP production and utilization, all of which play
a central role in the cerebral bioenergetics and function in nor-
mal and diseased brains. Development of in vivo tools being able
