9/18/2023 0 Comments Cyclic amp glucose![]() ![]() It is in this catalytic domain where AMPK becomes activated when phosphorylation takes place at threonine-172 (on α1 isoform) or Thr-174 (on α2 isoform) by an upstream AMPK kinase ( AMPKK). As AMP binds both Bateman domains the γ subunit undergoes a conformational change which exposes the catalytic domain found on the α subunit. Binding of one AMP to a Bateman domain cooperatively increases the binding affinity of the second AMP to the other Bateman domain. The four CBS domains create two binding sites for AMP commonly referred to as Bateman domains. AMPK is deactivated upon AMP displacement by ATP at CBS site 3, suggesting CBS3 to be the primary allosteric regulatory site. Specifically, the γ subunit includes four particular Cystathionine-β-synthase (CBS) domains, giving AMPK its ability to sensitively detect shifts in the AMP/ ATP ratio. ![]() Each of these three subunits takes on a specific role in both the stability and activity of AMPK. Structure ĪMPK is a heterotrimeric protein complex that is formed by α, β, and γ subunits. It should not be confused with cyclic AMP-activated protein kinase ( protein kinase A). In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreatic β-cells. ![]() It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. It consists of three proteins ( subunits) that together make a functional enzyme, conserved from yeast to humans. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. ![]()
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