Intracellular ATP concentrations must be maintained within a narrow range to sustain appropriate metabolic function. Recent evidence indicates that the coordination of this task is achieved through the AMP-activated protein kinase. This kinase is typically activated by an increase in the AMP:ATP ratio. In its active form, the AMPK regulates a large number of downstream targets that together lead to a reduction in anabolic pathways and a stimulation of catabolic pathways. The net result of AMPK AP24534 Src-bcr-Abl inhibitor activation is the stabilization of ATP levels and restoration of energy balance. The AMPK of mammals exists as a heterotrimeric complex consisting of a catalytic a subunit and two regulatory subunits b and c. The conventional serine/threonine kinase activity of AMPK is supported by the a subunit, which is characterized by the presence of a threonine residue activation loop whose phosphorylation is required for full activation. Homologues of all three subunits exist in mammals, invertebrates, yeast, plants and the primitive protozoa, with a high degree of conservation suggesting that this signaling pathway evolved over one billion years ago to regulate metabolic homeostasis, although the exact evolutionary dynamics of AMPK are unclear. The existence of AMPK is reported in several fish species including goldfish, zebrafish, crucian carp and salmon. Additionally, numerous submissions to gene databases complete the list of species in which this kinase is reported including puffer fish, stickleback, and the Japanese ricefish. Despite this apparent wide distribution in the piscine model, only a few studies have dealt with AMPK functions in fish or have established a phylogenetic relationship of AMPK subunits as found in fish and other vertebrates. Three different studies published nearly simultaneously addressed the role of AMPK in hypoxia-related functions all in hypoxic-insensitive cyprinids. However, the only information regarding the metabolic consequences of the activation of this kinase in fish reported an increased metabolic rate in anoxic crucian carp treated with the AMPK inhibitor Compound C ; thus, further studies on AMPK function are warranted. Mammalian AMPK is inactive unless phosphorylated by upstream kinases, with the critical phosphorylation site being Thr172 within the ����activation loop���� of the kinase domain within the a subunit. Either 59-AMP or the AICAR phosphorylated form activates AMPK by binding to the c subunit. This binding promotes phosphorylation by the upstream kinase, allosterically activates the phosphorylated kinase, and inhibits dephosphorylation of Thr172 by protein phosphatases. There are at least two signaling pathways upstream of AMPK: one is triggered by an increase in the AMP:ATP ratio and dependent on LKB1, and the other is triggered by an increase in Ca2+ and is dependent on CaMKKb. Winder and Hardie proposed that activators of AMPK may be effective Life Science Reagents treatments for type 2 diabetes.