Figure 1. Schematic showing role of AMPK in the regulation of cellular energy balance. Catabolism normally maintains a high ratio of ATP:ADP in the cell (typically 10:1). Inhibition of catabolism (e.g. starvation for glucose or oxygen), or acceleration of ATP consumption (e.g. muscle contraction) would cause an increase in the ADP:ATP ratio that is converted by the enzyme adenylate kinase into an even larger rise in AMP:ATP. Rising AMP coupled with falling ATP switches on the AMPK system, which then activates alternate catabolic pathways and switches off ATP-consuming processes to restore energy balance.

Figure 2. Structure of the core of the mammalian AMPK complex. For the protein, only the course of the polypeptide backbone is shown in ‘cartoon’ view; for AMP, atoms are shown as ‘spheres’, with carbon green, nitrogen blue, oxygen red, phosphorus orange and hydrogen omitted. The C-terminal domain of the subunit (yellow) is on the left, with the C-terminal region of the subunit (red) wrapping around it. The interaction between the complex and the subunits is mainly via the three-stranded -sheet at left centre, with two strands (red) from and one (blue-green) from . The structure contains the entire 1 subunit, with the N-terminal region in salmon pink followed by the four CBS repeats: CBS1 (blue-green), CBS2 (magenta), CBS3 (dark blue) and CBS4 (orange). Three molecules of AMP are present, one (AMP2) in the cleft between CBS1 and CBS2, and two (AMP1 and AMP3, the latter being nonexchangeable) in the cleft between CBS3 and CBS4. All three molecules of AMP are oriented with their phosphate groups towards the central aqueous channel, via which the nucleotides may enter and leave. The image was created using MacPyMol using published atomic coordinates (Xiao et al., 2007).

Figure 3. Summary of metabolic stresses, drugs and cytokines that regulate AMPK.