AMP-activated protein kinase â development of the energy sensor concept
The LKB1âAMPK cascade is switched on by metabolic stresses that either inhibit ATP production (e.g. hypoxia, hypoglycaemia) or that accelerate ATP consumption (e.g. muscle contraction). Any decline in cellular energy status is accompanied by a rise in the cellular AMP: ATP ratio, and this activate...
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Veröffentlicht in: | The Journal of physiology 2006-07, Vol.574 (1), p.7-15 |
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Sprache: | eng |
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Zusammenfassung: | The LKB1âAMPK cascade is switched on by metabolic stresses that either inhibit ATP production (e.g. hypoxia, hypoglycaemia)
or that accelerate ATP consumption (e.g. muscle contraction). Any decline in cellular energy status is accompanied by a rise
in the cellular AMP: ATP ratio, and this activates AMPK by a complex and sensitive mechanism involving antagonistic binding
of the nucleotides to two sites on the regulatory γ subunits of AMPK. Once activated by metabolic stress, AMPK activates catabolic
pathways that generate ATP, while inhibiting cell growth and biosynthesis and other processes that consume ATP. While the
AMPK system probably evolved in single-celled eukaryotes to maintain energy balance at the cellular level, in multicellular
organisms its role has become adapted so that it is also involved in maintaining whole body energy balance. Thus, it is regulated
by hormones and cytokines, especially the adipokines leptin and adiponectin, increasing whole body energy expenditure while
regulating food intake. Some hormones may activate AMPK by an LKB1-independent mechanism involving Ca 2+ /calmodulin dependent protein kinase kinases. Low levels of activation of AMPK are likely to play a role in the current global
rise in obesity and Type 2 diabetes, and AMPK is the target for the widely used antidiabetic drug metformin. |
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ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2006.108944 |