AMP-activated protein kinase (AMP-activated proteinkinase, AMPK) is the switch of the body's energy metabolism, and research on AMPK has developed rapidly in recent years. The glycogen-binding domain (GBD) region was found in the β subunit, and the CBS region was found in the gamma subunit, and their functions were studied. The activity of AMPK is regulated by AMP in three different ways in the body. It has been found in mammals that AMPK is regulated by its upstream kinase LKB1, and AMPK's regulation of the body is not only reflected in energy metabolism, but also includes gene expression, protein translation, and cell growth.

Figure 1. Protein structure of AMPK.

Introductions

AMPK, a heterotrimeric protein, consists of three subunits α, β and γ. These three subunits are contained in eukaryotes with known gene sequences. These three subunits are controlled by 2 to 3 independent genes (α 1, α 2; β1, β2; γ 1, γ 2, γ 3), and different subunits can be arranged and combined to form different AMPK complexes. The study found that the enzyme exists in primitive eukaryotes without mitochondria, nucleoli and peroxisomes, indicating that the inclusion of AMPK is a universal feature of all eukaryotes.

Regulation of AMPK complex vitality

AMP can activate AMPK through the following three different pathways, all of which can be inhibited by ATP.

1. AMP directly acts on AMPK, and allosteric activates AMPK. A large number of such allosteric adjustments can increase AMPK activity by less than 5 times.
2. The combination of AMP and AMPK makes it a good substrate for its upstream kinases. Its upstream kinase specifically activates AMPK by phosphorylating 172 threonine residues of the α subunit of AMPK, and then activates other protein kinases. This phosphorylation causes at least a 50 to 100-fold change in AMPK activity. Studies have found that when the corresponding threonine residues of yeast are changed, they cause the loss of all functions, and it is certain that this regulation is conserved in all eukaryotic cell organisms.
3. AMP and AMPK binding inhibit the threonine residue at position 172 of the α subunit by protein kinase dephosphorylation. This regulatory effect is already present in higher plants. Intracellular AMP regulates the activity of AMPK through three different pathways. It is an ultra-sensitive method. When the AMP concentration changes very slightly, it can cause great changes in AMPK activity.

AMPK metabolic regulation

There are many studies and reviews on AMPK and metabolic regulation. In recent years, the following important progress has been made: Recent studies have shown that AMPK adjusts blood glucose levels, fatty acid oxidation and glycogen metabolism in Studies that play an important role in the overall energy balance of the body show that intraperitoneal injection of leptin causes time-dependent changes in AMPK, thereby achieving regulation of human diet. This suggests that the control of AMPK activity may achieve the purpose of treating metabolic disorders such as obesity and type 2 diabetes. The large consumption of ATP during exercise activates AMPK on the one hand and improves its vitality; on the other hand, it increases the glucose uptake of skeletal muscle through the translocation of GLUT4 (glucose transport 4). Recently, a lot of research has been conducted on whether the activation of AMPK is necessary for GLUT4 translocation, but the results obtained are not consistent. Therefore, a lot of research on the impact of AMPK on GLUT will be necessary in the future.

Conclusions

AMPK, as the body's energy metabolism switch, is mainly regulated by changes in the body's AMP: ATP ratio, which is one of the body's sensitive energy regulation mechanisms. With the research progress of the structure of the γ subunit of AMPK, the specific mechanism of AMP joining to AMPK becomes clearer. LKB1 is an upstream signal of AMPK determined by recent research, and it is also a tumor suppressor. It is suggested that AMPK may be related to cell polarity, cell growth and differentiation. The regulation of intracellular protein expression by AMPK has only been noticed in recent years, but its development is very rapid. It has been found that AMPK can regulate gene expression, affect mRNA stability, and inhibit protein expression. AAMPK's research is leading to a deeper field, and it is no longer possible to be just a cell energy switch. Its role in regulating cell protein metabolism, research on the body's overall energy metabolism, and cell growth and differentiation suggest that AMPK is a participant in many life processes of the body.

References:

1. Stapleton D; et al. Mammalian AMP-activated protein kinase subfamily. J Biol Chem., 1996;271(2):611-4.