AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart
- PMID: 22043210
- PMCID: PMC3083815
- DOI: 10.2174/157340310793566073
AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart
Abstract
Adenosine monophosphate - activated kinase (AMPK) plays a key role in the coordination of the heart's anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating β - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ - subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.
Keywords: AMPK; Adenosine monophosphate - activated protein kinase; cardiac energy metabolism.; heart failure.
Figures
![Fig. (1)](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3083815/bin/CCR-6-337_F1.gif)
![Fig. (2)](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3083815/bin/CCR-6-337_F2.gif)
Acetyl-CoA carboxylase
Fatty acid binding protein
Fatty acid transporter (CD36)
![Fig. (3)](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3083815/bin/CCR-6-337_F3.gif)
Hexokinase
Phospofructokinase
Pyruvatkinase
Glucosetransporter
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References
-
- Carlson CA, Kim KH. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem. 1973;248(1):378–80. - PubMed
-
- Arad M, Seidman CE, Seidman JG. AMP-activated protein kinase in the heart: role during health and disease. Circ Res. 2007;100(4):474–88. - PubMed
-
- Allard MF, Parsons HL, Saeedi R, Wambolt RB, Brownsey R. AMPK and metabolic adaptation by the heart to pressure overload. Am J Physiol Heart Circ Physiol. 2007;292(1):H140–8. - PubMed
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