AMPK plays a key role in the regulation of energy homeostasis. It acts as a metabolic stress-inducing protein kinase that switches off biosynthetic pathways when cellular ATP levels are low and when 5`-AMP rises in response to fuel limitation. AMPK is activated by high AMP and low ATP via a mechanism that involves allosteric regulation, promotion of phosphorylation by an upstream protein kinase known as AMPK kinase, and inhibition of dephosphorylation. Activated AMPK can phosphorylate and regulate in vivo hydroxymethylglutaryl-CoA reductase and acetyl-CoA carboxylase. May increase the rate of glucose oxidation in muscle by increasing the rate of glucose transport. Shows homology to yeast protein kinase-encoding gene (snf1) regulating carbohydrate metabolism. Human AMPKg2 is a 569 aa protein, which contains unique N-terminal domains and participate in binding of AMP within the AMPK complex. AMPK is a heterotrimeric complex composed of a catalytic subunit and two regulatory subunits. Three isoforms of the gamma subunit exist in the brain with gamma 2 and gamma 3 present, which is distinct from the rat liver gamma 1 isoform. The noncatalytic subunits of AMPK are related to proteins that interact with snf1p; the beta subunit is related to the SIP1/SIP2/ GAL83 family of transcription regulators and the gamma subunit to SNF4.3 Mutations in AMPKgamma 2 can cause familial hypertrophic cardiomyopathy (HCM), which provides evidence for the central role of energy compromise in disease pathogenesis.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.