Fig. 4.

NDPK substrate channelling hypothesis: ATP produced by nucleoside diphosphate kinase (NDPK), from GTP and ADP, is used by the AMP-activated protein kinase (AMPK) as substrate in the AMPK-mediated phospho-transfer reaction. AMPK then uses this NDPK-mediated substrate to phosphorylate its downstream targets, one example of which is acetyl-CoA carboxylase 1 (ACC1). Accumulation of ADP as a result of AMPK phospho-transfer could potentially feed back to NDPK in the microenvironment and fuel the generation of more ATP. By this rationale, even under extremely limiting ATP concentrations, NDPK would provide substrate ATP to AMPK by proxy of their tight association, allowing AMPK to remain functional despite a general shortage of cellular ATP. Thus, NDPK has a role to play in the AMPK signalling cascade. Schematic diagram is based on the observations in Figs. 4 and 5, hypothesising the interaction of NDPK with AMPK taking into account the fates of ADP, GTP and ATP pertaining to the ability of AMPK to phosphorylate ACC1, a major downstream components of the AMPK signalling cascade. Reproduced with permission from Biochem. J.