GTP:AMP phosphotransferase AK3, mitochondrial

AK3 is a mitochondrial adenylate kinase that catalyzes GTP:AMP phosphotransferase activity, recycling GTP into GDP within the mitochondrial matrix to support the TCA cycle (UniProt: Q9UIJ7). The enzyme can also utilize ITP as an alternative phosphate donor and is localized to the mitochondria where energy metabolism is tightly regulated.

AK3 expression is upregulated in Alzheimer's Disease brain tissue. Analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) revealed increased AK3 levels with a mean log2 fold-change of 0.30 (Chaparral AD proteomics). This upregulation may reflect compensatory metabolic responses to mitochondrial dysfunction observed in AD pathology.

The functional role of AK3 in mitochondrial energy metabolism suggests its upregulation could represent an attempt to sustain ATP and GTP production under the bioenergetic stress characteristic of Alzheimer's Disease neurodegeneration.