Malate is transported into the mitochondrial matrix while a-ketoglutarate is
transported out by the malate-a-ketoglutarate antiporter, a seeming mass
unbalance. Next malate is oxidized back to oxaloacetate producing NADH
from NAD+ in the mitochondrial matrix by mitochondrial malate dehydroge-
nase. Oxaloacetate cannot be transported per se across the mitochondrial
membrane. It is, instead transaminated to aspartate from the NH3 donor gluta-
mate by mitochondrial glutamate-oxaloacetate transaminase. Aspartate is
transported out of the matrix whereas glutamate is transported in by the
glutamate-aspartate antiporter in the mitochondrial membrane, obviating the
apparent mass unbalance noted above. The last step of the shuttle is catalyzed
by cytosolic glutamate-oxaloacetate transaminase regenerating cytosolic
oxaloacetate from aspartate and cytosolic glutamate from a-ketoglutarate both
of which were earlier transported in opposing directions by the malate-a-
ketoglutarate antiporter. The net effect of this shuttle is to transport electrons
from cytosolic NADH to mitochondrial NAD+. Therefore, those electrons can
be presented by the newly formed NADH to electron transport system com-
plex I thereby producing three ATPs by oxidative phosphorylation. Note that
depending on which shuttle is used (i.e., which tissue is catalyzing glycolysis)
either two or three extra ATPs are produced by oxidative phosphorylation per
triose phosphate going through the latter steps of glycolysis.
In nonaerobic glycolysis, as in the case when a tissue is subjected to an
ischemic episode (i.e., myocardial infarction), neither the extra ATP produced
by the shuttle nor the ATPs produced by normal passage of electrons through
the electron transport chain are produced because of oxygen insufficiency.
Therefore glycolysis must increase in rate to meet the energy demand. In dam-
aged tissue this increased rate is compromised. Moreover the shuttle mecha-
nisms to regenerate NAD+ from NADH formed by glycolysis are unavailable,
as shown in Figure 27-4. Glycolysis under ischemic conditions satisfies the
requirement for NAD+ by reducing pyruvate, the glycolytic end product under
normative conditions, to lactate with the reducing equivalents of NADH.
The new end product lactate accumulates in muscle cells under ischemic
conditions and damages cell walls with its low pH causing rupture and loss of
cell contents such as myoglobin and troponin I. These compounds as well as
other end products combine to cause increased cell rupture and pain.
Reopening vasculature by reperfusion as rapidly as possible is a first step
in treatment. Thrombolysis within an hour after infarction gives best results.
Supportive measures, regulation of heart rate and pressure are required fol-
lowing the infarction to allow recovery from the ischemic episode and repair
of tissue damage. Nutritional monitoring is required both for tissue repair and
prevention of recurrence.