5’-AMP-activated protein kinase (AMPK), a trimeric enzyme in mammals, consists of a catalytic α subunit (63 kDa) and the non-catalytic ß and γ subunits. The N-terminal of the α subunit contains a serine/threonine kinase catalytic domain. The ß and γ subunits interact with the C-terminal region of the α subunit. There are two genes that encode isoforms of both the α and ß subunits (α1, α2, ß1 and ß2) and three genes encode isoforms of the γ subunit (γ1-γ3). The α2 isoform is found predominantly in skeletal and cardiac muscle. Hepatic tissue exhibits an equal distribution of both α1 and α2 isoforms, and in pancreatic ß-cells largely the α1 is expressed.
AMPK is activated by increases in the cellular AMP/ATP ratio caused by metabolic stress that either interfere with ATP production or accelerates ATP consumption. AMP affects AMPK by a direct allosteric activation thereby making it a poor substrate for dephosphorylation. Even a small increase in AMP levels can induce a significant increase in the activity of AMPK. AMPK is activated by phosphorylation at Thr172 in the activation loop by one or more upstream AMPK kinases, including Akt. LKB1, an upstream constitutively active protein kinase, phosphorylates AMPK when AMP levels are elevated in cells. In addition, Ca2+/CaM kinase ß is shown to phosphorylate and activate AMPK when calcium levels are increased, independent of any increase in AMP levels.
AMPK stimulates pathways that are linked to increased energy production, such as glucose transport and fatty acid oxidation. On the other, hand it switches off the energy consuming pathways, such as lipogenesis, protein synthesis, and gluconeogenesis.
References:
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Kahn, B.B., et al. 2004. Cell Metab. 1, 15.
Rutter, G.A. et al. 2003. Biochem. J. 375, 1.
