AMP‐activated protein kinase: the energy charge hypothesis revisited

@article{Hardie2001AMPactivatedPK,
  title={AMP‐activated protein kinase: the energy charge hypothesis revisited},
  author={David Grahame Hardie and Simon A. Hawley},
  journal={BioEssays},
  year={2001},
  volume={23}
}
The AMP‐activated protein kinase cascade is a sensor of cellular energy charge, and its existence provides strong support for the energy charge hypothesis first proposed by Daniel Atkinson in the 1960s. The system is activated in an ultrasensitive manner by cellular stresses that deplete ATP (and consequently elevate AMP), either by inhibiting ATP production (e.g., hypoxia), or by accelerating ATP consumption (e.g., exercise in muscle). Once activated, it switches on catabolic pathways, both… 
Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status.
TLDR
The AMPK cascade is the probable target for the antidiabetic drug metformin, and current indications are that it is responsible for many of the beneficial effects of exercise in the treatment and prevention of type 2 diabetes and the metabolic syndrome.
The AMP-activated protein kinase pathway – new players upstream and downstream
TLDR
The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy status and regulates food intake and energy expenditure at the whole body level, in particular by mediating the effects of hormones and cytokines such as leptin, adiponectin and ghrelin.
AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
TLDR
Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level.
AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels.
  • D. Hardie
  • Biology
    Annual review of nutrition
  • 2014
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose
AMPK: a cellular energy sensor primarily regulated by AMP.
TLDR
It is found that only mechanism (ii) is mimicked by ADP, and that ADP is also less potent than AMP, which the authors believe to be the primary signal.
AMP-activated protein kinase, stress responses and cardiovascular diseases.
TLDR
Recent literature is reviewed showing that AMPK functions far beyond its proposed energy sensor and regulator function, and regulates ROS, autophagy, cell proliferation, cell apoptosis, cellular polarity, mitochondrial function and genotoxic response.
AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer.
  • D. Hardie
  • Biology
    Biochemical Society transactions
  • 2011
TLDR
AMPK has become a key drug target to combat metabolic disorders associated with overnutrition such as Type 2 diabetes, and some existing anti-diabetic drugs and many 'nutraceuticals' work by activating AMPK, usually via inhibition of mitochondrial ATP production.
AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer
TLDR
It is essential to life that a balance is maintained between processes that produce ATP and those that consume it, and systems that monitor the levels of ATP and ADP, although because of the adenylate kinase reaction, AMP is actually a more sensitive indicator of energy stress than ADP.
Mechanisms of activation and inhibition of the metabolic regulator AMP-activated protein kinase (AMPK)
TLDR
Results demonstrate that measuring adenine nucleotide ratios is fundamental to distinguish novel mechanisms from canonical mechanisms of intracellular AMPK regulation.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 67 REFERENCES
The AMP‐Activated Protein Kinase
TLDR
The central hypothesis is that the AMP-activated protein kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress, and protects the cell by switching off ATP-consuming pathways and switching on alternative pathways for ATP generation.
Dual regulation of the AMP‐activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle
TLDR
The novel regulation of AMPK described here provides a mechanism by which energy supply can meet energy demand following the utilization of the immediate energy reserve provided by the creatine kinase–phosphocreatine system.
AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge.
TLDR
It is shown that the AMP-activated protein kinase cascade responds in intact cells in an ultrasensitive manner over a critical range of nucleotide concentrations, in that only a 6-fold increase in activating nucleotide is required in order for the maximal activity of the kinase to progress from 10% to 90%, equivalent to a co-operative system with a Hill coefficient of 2.5.
The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell?
TLDR
AMP-activated protein kinase and SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.
AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes.
  • W. Winder, D. Hardie
  • Biology, Medicine
    American journal of physiology. Endocrinology and metabolism
  • 1999
TLDR
Increased recruitment of the AMPK signaling system, either by exercise or pharmaceutical activators, may be effective in correcting insulin resistance in patients with forms of impaired glucose tolerance and Type 2 diabetes resulting from defects in the insulin signaling cascade.
5‐Aminoimidazole‐4‐Carboxamide Ribonucleoside
TLDR
AICAR provides direct evidence that the inhibition by AMPK of activation of hormone-sensitive lipase by cyclic-AMP-dependent protein kinase also operates in intact cells, and should be a useful tool for identifying new target pathways and processes regulated by theprotein kinase cascade.
...
1
2
3
4
5
...