Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5′-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5′-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes. A new study published in a recent issue of Biochemical Journal by Zibrova et al. shows that glutamine:fructose-6-phosphate amidotransferase-1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), is a physiological substrate of AMPK. The HBP is an offshoot of the glycolytic pathway that drives the synthesis of uridine-5′-diphospho-N-acetylglucosamine, the requisite donor metabolite needed for dynamic β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of cellular proteins. O-GlcNAcylation is a nutrient-sensitive post-translational modification that, like phosphorylation, regulates numerous intracellular processes. Zibrova et al. show that inhibitory phosphorylation of the GFAT1 residue Ser243 by AMPK in response to physiological or small-molecule activators leads to a reduction in cellular protein O-GlcNAcylation. Further work revealed that AMPK-dependent phosphorylation of GFAT1 promotes angiogenesis in endothelial cells. This elegant study demonstrates that the AMPK–GFAT1 signaling axis serves as an important communication point between two nutrient-sensitive signaling pathways and is likely to play a significant role in controlling physiological processes in many other tissues.
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April 2017
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Cover Image
Structure of O-acetylserine sulfhydrylase (OASS) from Brucella abortus compared with all known OASS structures. The high degree of variation is observed in N-terminal domain, which determined the size of active site cleft and responsible for interactions with Serine acetyl Transferase. The co-factor Pyridoxal phosphate (PLP) is shown in ball & stick model in the active site. For more information, please see study by Dharavath et al. in this issue, pages 1221–1239. Image provided by Samudrala Gourinath.
Commentary|
March 23 2017
The sweet side of AMPK signaling: regulation of GFAT1
John W. Scott;
1St Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia
2Mary MacKillop Institute for Health Research, Australian Catholic University, 215 Spring Street, Melbourne 3000, Australia
Correspondence: John W. Scott (jscott@svi.edu.au)
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Jonathan S. Oakhill
Jonathan S. Oakhill
1St Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia
2Mary MacKillop Institute for Health Research, Australian Catholic University, 215 Spring Street, Melbourne 3000, Australia
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Publisher: Portland Press Ltd
Received:
February 09 2017
Revision Received:
February 13 2017
Accepted:
February 15 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (7): 1289–1292.
Article history
Received:
February 09 2017
Revision Received:
February 13 2017
Accepted:
February 15 2017
Connected Content
This is a commentary on:
GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis
Citation
John W. Scott, Jonathan S. Oakhill; The sweet side of AMPK signaling: regulation of GFAT1. Biochem J 1 April 2017; 474 (7): 1289–1292. doi: https://doi.org/10.1042/BCJ20170006
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