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Maintaining Energy Balance in Health and Disease: Role of the AMP-Activated Protein Kinase

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Book cover Post-Translational Modifications in Health and Disease

Part of the book series: Protein Reviews ((PRON,volume 13))

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Abstract

Maintaining a steady balance between energy production and consumption is a cornerstone of all living cells. Failure to maintain this balance affects most, if not all, cellular activities as these processes are normally tightly coupled to the energy status of the cell. It is beginning to emerge that human diseases such as obesity, Type 2 diabetes, and even certain types of cancer may be linked to underlying defects in the regulation of energy balance. Since the evolution of eukaryotes, the AMP-activated protein kinase (AMPK) system has played a pivotal role in maintaining energy homeostasis by regulating the enzymes that control flux through virtually every branch of metabolism. AMPK functions primarily as a fuel gauge monitoring the ratio of AMP to ATP, which can be regarded as a molecular read-out of cellular energy status. It becomes activated when energy utilisation overtakes energy production, and serves to rectify this imbalance by upregulating ATP-producing pathways while switching off ATP-consuming pathways such as lipid, carbohydrate and protein biosynthesis. In addition to regulating energy balance at the cellular level, AMPK is also a central regulator of whole-body energy homeostasis, integrating a variety of hormonal and nutritional signals in the central nervous system and periphery to control feeding behaviour and body weight. Increasing our understanding of the regulation and physiological roles of AMPK promises to open new avenues for the treatment of a whole range of debilitating human diseases.

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Abbreviations

AMPK:

AMP-activated protein kinase

ACC:

Acetyl CoA carboxylase

AMP:

Adenosine 5’-monophosphate

ATP:

Adenosine 5’-triphosphate

CaMKK:

Ca2+/calmodulin dependent protein kinase kinase

CBS:

Cystathionine-β-synthase domain

CBM:

Carbohydrate-binding module

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Acknowledgements

I would like to thank Prof Bruce Kemp for mentoring and helpful discussions. This work was funded by the Australian Research Council and the National Health and Medical Research Council.

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  1. St Vincent’s Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy, 3065, VIC, Australia

    John W. Scott

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  1. Depto. Quimica Inorganica, Universidad Murcia, Murcia, Spain

    Cecilio J. Vidal

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Scott, J.W. (2011). Maintaining Energy Balance in Health and Disease: Role of the AMP-Activated Protein Kinase. In: Vidal, C. (eds) Post-Translational Modifications in Health and Disease. Protein Reviews, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6382-6_9

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