ABSTRACT
AMP-activated protein kinase (AMPK) was rst described in 1989 (Hardie et al. 1989). Since then, interest in AMPK has exploded due to its apparent association with obesity and diabetes (Hardie 2007). AMPK is a heterotrimeric complex comprising a catalytic subunit (α) and two regulatory subunits (β and γ). The approximate molecular masses are 63 and 38 kDa for the α-and β-subunits, respectively (Hardie and Carling 1997; Hardie et al. 1998; Winder and Hardie 1999). The γ-subunit
10.1 Introduction .......................................................................................................................... 195 10.2 Mechanisms Controlling AMPK Activation ........................................................................ 196
10.2.1 Allosteric Activation by AMP .................................................................................. 196 10.2.2 AMPK Kinases, Phosphatase, and AMPK α-Subunit Phosphorylation at Thr
172 ............................................................................................................................. 196 10.2.2.1 AMPK Phosphorylation at Thr 172 and Activation ................................... 196 10.2.2.2 LKB1 as an Upstream Activator of AMPK ............................................... 196 10.2.2.3 Ca2+/Calmodulin-Dependent Protein Kinase Kinase (CaMKK) as
AMPKK ..................................................................................................... 197 10.2.2.4 Other Proposed AMPKK ........................................................................... 197 10.2.2.5 Phosphatase ................................................................................................ 197
10.3 AMPK Activity Is Regulated by Hormones and Cytokines, and Drugs .............................. 197 10.3.1 Hormone and Cytokine Regulation of AMPK Activity ........................................... 197 10.3.2 Pharmacological Activation of AMPK ..................................................................... 198
10.4 AMPK in Muscle Growth and Development........................................................................ 199 10.4.1 AMPK and Muscle Protein Synthesis ...................................................................... 199 10.4.2 AMPK and Muscle Protein Degradation .................................................................. 201
10.5 AMPK in Adipogenesis and Fat Accumulation ................................................................... 201 10.5.1 AMPK in Lipid Metabolism ..................................................................................... 201 10.5.2 AMPK and Adipogenesis .........................................................................................202