AMPK

AMPK

One of the central regulators of cellular and organismal metabolism in eukaryotes is the AMP-activated protein kinase (AMPK), which is activated when intracellular ATP levels lower. AMPK plays critical roles in regulating growth and reprogramming metabolism, and recently has been connected to cellular processes including autophagy and cell polarity. It consists of three proteins (subunits) that together make a functional enzyme.

Adenosine monophospate-activated protein kinase (AMPK) is a master sensor and regulator of energy balance in living organisms. Highly conserved in eukaryotes, mammalian AMPK is a heterotrimeric protein, comprising of two catalytic alpha subunits (alpha 1-2), two beta (beta 1-2), and three gamma regulatory subunits (gamma 1-3). The alpha subunits contain the catalytic serine-threonine kinase domain where AMPK is phosphorylated by upstream kinases, specifically at the Threonine 172 (Thr172) site. Mutation of this site results in a loss of function of AMPK (dominant negative). Tissues from AMPK-deficient mice provide evidence that the catalytic alpha2 subunit, not alpha1, is the major subunit involved in glucose uptake in muscle, especially in response to AMPK agonists. However, the alpha1 subunit may play some role in glucose uptake in response to twitch contraction. In fact, most models of AMPK deficiency possess mutations to the alpha2 catalytic subunit due to its more pronounced phenotype. The AMPK beta subunits contain a glycogen binding domain (GBD), allowing for localization of AMPK to glycogen, which may regulate its activity. The gamma subunits contain four tandem repeats of a sequence motif, otherwise known as the CBS or Bateman domains. These motifs contain regulatory AMP- and ATP- binding sites, which bind these nucleotides in a cooperative manner.

AMPK affects a number of metabolic processes in different mammalian tissues, such as the liver, pancreas, muscle, heart, adipose tissues, and the central nervous system (CNS). AMPK generally stimulates energy production by increasing catabolic pathways and conversely inhibiting anabolic pathways. AMPK also produces both translational and transcriptional effects through phosphorylation of its targets or through nuclear localization. Recent research has implicated a role for AMPK in adaptive metabolic reprogramming through transcriptional regulation. Abnormalities in AMPK function have been implicated in a number of and . Induction of autophagy has been associated with the beneficial effects endowed by caloric restriction and exercise to aging.

Reference:Maria A. G. Lim. THE CONTRIBUTION OF METABOLIC DYSFUNCTION TO GENETIC MODELS OF MOTOR NEURON DISEASE

Products for AMPK

Price Inquiry
© 2017 MuseChem - A division of ArrakisTek Inc. All Rights Reserved.