Humpath.com - Human pathology

Home > A. Molecular pathology > AMPK

AMPK

Friday 7 January 2005

AMPKs, SNF1/AMP-activated protein kinase (AMPK) family

Definition : The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels.

When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation.

The AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells.

The mammalian 5-prime-AMP-activated protein kinase (AMPK) appears to play a role in protecting cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways.

AMPK is a heterotrimeric protein composed of 1 alpha subunit, 1 beta subunit (e.g., PRKAB1; MIM.602740), and 1 gamma subunit (e.g., PRKAG1; MIM.602742). The catalytic alpha subunit requires phosphorylation for full activity.

It is related to the S. cerevisiae Snf1 protein kinase, which is involved in the response to nutritional stress.

The noncatalytic beta and gamma subunits are related to yeast proteins that interact with Snf1: the beta subunit to the Sip1/Sip2/Gal83 family of transcription regulators, and the gamma subunit to Snf4, which is thought to be an activator of Snf1.

Subunits

PRKAA1 PRKAA2 PRKAB1 PRKAB2 PRKAG1 PRKAG2 PRKAG3

Functions

- AMP-activated protein kinase (AMPK) plays a key role in the regulation of fatty acid and cholesterol metabolism. In vitro, it phosphorylates and inactivates 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)(MIM.142910) and acetyl-CoA carboxylase (ACC) (MIM.200350), key enzymes involved in regulating de novo biosynthesis of cholesterol and fatty acids, respectively.

Pathology

- PRKAG2 germline mutations in glycogen storage cardiomyopathy

- Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. (30022161)

References

- Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85. PMID: 17712357

- Barnes BR, Zierath JR. Role of AMP—activated protein kinase in the control of glucose homeostasis. Curr Mol Med. 2005 May;5(3):341-8. PMID: 15892653

- Hardie DG. New roles for the LKB1—>AMPK pathway. Curr Opin Cell Biol. 2005 Apr;17(2):167-73. PMID: 15780593