In mammalian cells aerobic oxidatio

In mammalian cells aerobic oxidation of glucose requires reducing equivalents produced in glycolytic
phase to be channelled into the phosphorylating respiratory chain for the reduction of molecular oxygen.
Data never presented before show that the oxidation rate of exogenous NADH supported by the malate–
aspartate shuttle system (reconstituted in vitro with isolated liver mitochondria) is comparable to the
rate obtained on activation of the cytosolic NADH/cytochrome c electron transport pathway. The activities
of these two reducing equivalent transport systems are independent of each other and additive.
NADH oxidation induced by the malate–aspartate shuttle is inhibited by aminooxyacetate and by rotenone
and/or antimycin A, two inhibitors of the respiratory chain, while the NADH/cytochrome c system
remains insensitive to all of them. The two systems may simultaneously or mutually operate in the transfer
of reducing equivalents from the cytosol to inside the mitochondria. In previous reports we suggested
that the NADH/cytochrome c system is expected to be functioning in apoptotic cells characterized by the
presence of cytochrome c in the cytosol. As additional new finding the activity of reconstituted shuttle
system is linked to the amount of a-ketoglutarate generated inside the mitochondria by glutamate dehydrogenase
rather than by aspartate aminotransferase.