In: Chemistry
pMice that are completely lacking the Adenine nucleotide translocase gene (Ant-/-) are viable (which is surprising) and show the following physiological phenotypes:
nHighlevels of alanine, lactate and succinate (in serum).
nAsix-fold increase of mitochondrial hydrogen peroxide as compared with normal control mice.
pGive reasonable biochemicalexplanations to each of these observations.
Adenine nucleotide translocase (ANT) is an enzyme that catalyses the exchange of ADP / ATP across the mitochondrial membrane. This constitutes about 10% of mitochondrial protein. Under respiring conditions, ATP generated by oxidative phosphorylation is exported to the cytosol for use in cellular activities and ADP is imported into the mitochondrial matrix for continuous ATP synthesis. In ANT deficiency conditions, ADP/ATP exchange does not occur across mitochondrial membrane resulting in the impairment of cellular activities. The metabolites accumulate in the cell.
Here in mice, pyruvate produced by glycolysis is converted to alanine by transamination. Also, pyruvate finds another path to be reduced to lactate. Since the metabolites in TCA cycle is not converted to final products, succinate is in higher level in serum. Lack of ADP in inner mitochondrial membrane for the synthesis of ATP leads to the inefficiency of the cell to carry out cellular activities.
It is conventionally thought that mitochondria contribute to ageing mainly through the overproduction of reactive oxygen species (ROS) and underproduction of ATP in aged cells. ANT enzyme has a major role in the apoptosis pathway. Since the ROS is not catabolized, it results in higher levels of H2O2 in mitochondrion.