AMPactivated

AMPactivated is a descriptive term used to denote the activated state of AMP-activated protein kinase (AMPK), a highly conserved serine/threonine kinase that serves as a cellular energy sensor. While AMPK is the enzyme, AMPactivated refers to AMPK when it has detected low energy status and is catalytically active, undergoing phosphorylation and conformational changes that enable downstream signaling. The term does not refer to a separate protein.

AMPK is a heterotrimer comprising α catalytic, β regulatory, and γ regulatory subunits. Activation occurs when cellular AMP or ADP levels rise relative to ATP, due to energy stress such as exercise, ischemia, or nutrient deprivation. AMP binding to the γ subunit allosterically activates AMPK and promotes phosphorylation of Thr172 in the α-subunit by upstream kinases LKB1, and CaMKKβ in response to calcium signals. Dephosphorylation by protein phosphatases returns AMPK to an inactive state.

Once AMPactivated, AMPK modulates metabolism by inhibiting energy-consuming anabolic pathways (lipogenesis, protein synthesis via mTORC1) and activating catabolic pathways (glycolysis, fatty acid oxidation, autophagy). It also regulates mitochondrial biogenesis and glucose uptake via GLUT4 translocation in skeletal muscle. These effects help restore cellular energy balance.

Physiological and clinical relevance: AMPK activation contributes to insulin sensitivity, weight maintenance, and endurance adaptations. Dysregulation is linked to metabolic diseases such as obesity and type 2 diabetes; pharmacologic activators (metformin, AICAR, salicylates; natural compounds) are areas of research.

Limitations: AMPK signaling is context dependent; activation of AMPK in different tissues can have distinct outcomes. The term AMPactivated appears mainly in educational or interpretive frameworks rather than as a formal nomenclature in peer-reviewed literature.