that show that localized regions of a protein unfold during conformational transitions. This mechanism reduces the strain and enhances catalytic efficiency. Local unfolding is the result of competing strain energies in the protein. The local (thermodynamic) stability of the substrate-binding domains ATPlid and AMPlid has been shown to be significantly lower when compared with the CORE domain in ADKE. coli. Furthermore, it has been shown that the two subdomains (ATPlid and AMPlid) can fold and unfold in a "non-cooperative manner." Binding of the substrates causes preference for 'closed' conformations amongst those that are sampled by ADK. These 'closed' conformations are hypothesized to help with removal of water from the active site to avoid wasteful hydrolysis of ATP in addition to helping optimize alignment of substrates for phosphoryl-transfer. Furthermore, it has been shown that the apoenzyme will still sample the 'closed' conformations of the ATPlid and AMPlid domains in the absence of substrates. When comparing the rate of opening of the enzyme (which allows for product release) and the rate of closing that accompanies substrate binding, closing was found to be the slower process. Function Metabolic monitoring The ability for a cell to dynamically measure energetic levels provides it with a method to monitor metabolic processes. By continually monitoring and altering the levels of ATP and the other adenyl phosphates (ADP and AMP levels) adenylate kinase is an important regulator of energy expenditure at the cellular level. As energy levels change under different metabolic stresses adenylate kinase is then able to generate AMP; which itself acts as a signaling molecule in further signaling cascades. This generated AMP can, for example, stimulate various AMP-dependent receptors such as those involved in glycolytic pathways, K-ATP channels, and 5' AMP-activated protein kinase (AMPK). Common factors that influence adenine nucleotide levels, and therefore ADK activity are exercise, stress, changes in hormone levels, and diet. It facilitates decoding of cellular information by catalyzing nucleotide exchange in the intimate “sensing zone” of metabolic sensors. ADK shuttle Adenylate kinase is present in mitochondrial and myofibrillar compartments in the cell, and it makes two high-energy phosphoryls (β and γ) of ATP available to be transferred between adenine nucleotide molecules. In essence, adenylate kinase shuttles ATP to sites of high energy consumption and removes the AMP generated over the course of those reactions. These sequential phosphotransfer relays ultimately result in propagation of the phosphoryl groups along collections of ADK molecules. This