Bypassing the glucose/fatty acid cycle: AMP-activated protein kinase.
The AMPK (AMP-activated protein kinase) cascade plays a key role in regulating energy metabolism. Conditions which cause a decrease in the ATP/AMP ratio lead to activation of AMPK. Once activated, AMPK initiates a series of responses that act to restore the energy balance of the cell. In skeletal muscle, activation of AMPK increases both glucose uptake and fatty acid oxidation, raising the possibility that AMPK can bypass the glucose/fatty acid cycle. This review focuses on the role of AMPK in the regulation of glucose and fatty acid metabolism in muscle. Recently, naturally occurring mutations within the gamma isoforms have been identified which lead to altered metabolic regulation in cardiac and skeletal muscle and suggest an important role for the kinase in regulating glycogen metabolism.
Carling
D
D
MRC Clinical Sciences Centre, Cellular Stress Group, Imperial College, Hammersmith Hospital Campus, DuCane Road, London W12 ONN, U.K. dcarling@csc.mrc.ac.uk
Fryer
L G D
LG
Woods
A
A
Daniel
T
T
Jarvie
S L C
SL
Whitrow
H
H
D055372:AMP-Activated Protein Kinases; D000595:Amino Acid Sequence; D004734:Energy Metabolism; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D009097:Multienzyme Complexes; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose