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AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge.

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  • 1. Biochemistry Department, Dundee University, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, Scotland, UK.
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    • Hardie DG 1
    (1 author)

ORCIDs linked to this article

The Biochemical Journal, 01 Mar 1999, 338 ( Pt 3):717-722
https://doi.org/10.1042/bj3380717 PMID: 10051444 PMCID: PMC1220108

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Abstract 

The AMP-activated protein kinase cascade is activated by elevation of AMP and depression of ATP when cellular energy charge is compromised, leading to inhibition of anabolic pathways and activation of catabolic pathways. Here we show that the system 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 (h) of 2.5. Modelling suggests that this sensitivity arises from two features of the system: (i) AMP acts at multiple steps in the cascade (multistep sensitivity); and (ii) the upstream kinase is initially saturated with the downstream kinase (zero-order ultrasensitivity).

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Biochem J. 1999 Mar 15; 338(Pt 3): 717–722.
PMCID: PMC1220108
PMID: 10051444

AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge.

D G Hardie, I P Salt, S A Hawley, and S P Davies
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Abstract

The AMP-activated protein kinase cascade is activated by elevation of AMP and depression of ATP when cellular energy charge is compromised, leading to inhibition of anabolic pathways and activation of catabolic pathways. Here we show that the system 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 (h) of 2.5. Modelling suggests that this sensitivity arises from two features of the system: (i) AMP acts at multiple steps in the cascade (multistep sensitivity); and (ii) the upstream kinase is initially saturated with the downstream kinase (zero-order ultrasensitivity).

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Selected References

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