ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise
Fig 1
Biochemical reactions are denoted by arrows and are labeled with a reaction number (r1, r2, etc.). Reversible reactions are indicated by double-sided arrows. Orange arrows depict nucleotide-binding reactions, and black arrows depict enzyme-catalyzed synthesis and degradation reactions. Species colored cyan represent unphosphorylated AMPK and species colored red represent phospho-AMPK. To simulate exercise, we changed the rate of the ATPase reaction (r1), which serves as the input to the model. The three modules of the model are distinguished by shading with the bioenergetic module shaded light blue, the AMPK regulatory module medium blue, and the activator module darker blue. The activator module is used to simulate the effects of two activators, ZMP and Compound 991 (C991). When simulating C991, only reactions r22 and r23, which represent reversible binding of C991 to AMPK and phospho-AMPK, are simulated in the activator module. When simulating the effects of ZMP, the module features r22 and r23 as well as r24 and r25, which represents the interconversion of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), the precursor molecule, to ZMP (r24) and ZMP degradation (r25). Activator-specific parameter values are used for r22 and r23.