AMP-activated protein kinase
From Wikipedia, the free encyclopedia
AMP-activated protein kinase or AMPK is consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans, that plays a role in cellular energy homeostasis. It is expressed in a number of tissues, including the brain, of mammals.
[edit] Structure
The three subunits are called alpha, beta and gamma. The alpha subunit contains the catalytic domain, an autoinhibitory domain and a subunit-binding domain. The beta subunit contains an N-terminal myristoylation group, a mid-molecule glycogen-binding domain and a C-terminal subunit interaction domain. The gamma subunit contain 4 repeats of the CBS domain that are predicted to bind AMP and ATP regulatory nucleotides.
[edit] Function
AMPK's primary role is the monitoring of energy use within cells. This kinase is allosterically activated by increased celluar AMP levels, a condition that occurs during cellular energy depletion. Upon activation, AMPK increases celluar energy levels by inhibiting anabolic energy consuming pathways (fatty acid synthesis, protein synthesis, etc.) and stimulating energy producing, catabolic pathways (fatty acid oxidation, glucose transport, etc.). Its activity has also been shown to be regulated by the adipocyte derived hormones leptin and adiponectin, although the mechanisms underlying this activation are currently unknown.
Recent research on mice at Harvard University, led by Barbara B. Kahn, has shown that when the activity of AMPK was inhibited, the mice ate less and lost weight. When AMPK levels were artificially raised the mice ate more and gained weight. Research in Britain has shown that the appetite-stimulating hormone ghrelin also affects AMPK levels.
A 2001 study (Zhou G et al) has indicated that the antidiabetic drug metformin (Glucophage®) acts by stimulating AMPK, leading to improved insulin resistance in the liver.
[edit] References
- Hardie, GH, Hawley, SA. AMP-Activated Protein Kinase: The Energy Charge Hypothesis Revisited. Bioessays. 2001. 23 (12) 1112-1119. PMID 11746230.
- Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004;428:569-74. PMID 15058305.
- Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167–1174. DOI 10.1172/JCI200113505.
