11.2 Sensing Energy Imbalances
KEY CONCEPTS
By the end of this section, you will be able to do the following:
- Apply your understanding of cell signalling pathways (Chapter 5.6) and enzyme regulation (Chapter 6.4) to explain how AMP-dependent kinase (AMPK) is involved in detecting energy imbalance.
- Evaluate how cellular changes under energy stress (Chapter 11.1) affect activity of AMPK signalling.
As explained in the previous section (Chapter 11.1), a variety of factors can lead to energy imbalances. For cells to combat energy stress, they must have a way to detect these imbalances. AMP-activated protein kinase (AMPK) is an important protein in signalling pathways that detect and respond to energy stress. Therefore, we will explore AMPK its role in sensing energy imbalances throughout this section.
AMP-activated protein kinase (AMPK)
In eukaryotic cells, sensing energy imbalances is done primarily through the AMP-activated protein kinase (AMPK) pathway (Figure 11.4). AMPK is an enzyme that is activated and inhibited depending on the relative abundance of AMP, ADP, and ATP. As described above, when the cell experiences an energy limitation, the concentration of AMP and ADP molecules rises because ATP is being hydrolyzed (consumed) at a faster rather than it is being synthesized. AMP and ADP molecules bind to AMPK, which activates this enzyme (Figure 11.4). AMPK is thus active under states of energy limitation, and inactive under states of energy excess. Other factors can also impact AMPK activity, including redox state (Figure 11.4). Active AMPK activates and inhibits various responses that help a cell increase ATP abundance (Chapter 11.3).
AMPK Structure and Function
AMPK is an enzyme composed of α, β, and γ subunits. The γ subunit can bind AMP, ADP, or ATP (Figure 11.5). For AMPK to be active, all three subunits must associate with each other (Figure 11.5). This is possible when the γ subunit is abound to AMP or ADP. This then promotes the phosphorylation of Thr172 (threonine at amino acid position #172) on the α subunit which increases AMPK activity by up to 100-fold inside the cell. When ATP to the γ subunit, Thr172 on the α subunit becomes dephosphorylated, causing this subunit to dissociate from AMPK, and a decrease in AMPK activity (Figure 11.5). AMPK is a kinase, so its primary mechanism of action is phosphorylating (adding phosphates to) other target proteins in the signalling pathways important for responding to energy stress.
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