AMP-activated protein kinase (AMPK) is a critical cellular energy sensor and regulator, playing a pivotal role in maintaining energy homeostasis at both cellular and whole-body levels. The structure of AMPK is a heterotrimeric complex composed of a catalytic α subunit and regulatory β and γ subunits. The γ subunit contains binding sites for AMP and ATP, which competitively bind to regulate the activity of the kinase. Activation of AMPK generally occurs through phosphorylation of its α subunit by upstream kinases, such as LKB1 (liver kinase B1) or CaMKKβ (calcium/calmodulin-dependent protein kinase kinase beta), which are themselves responsive to cellular energy levels and calcium signals, respectively.
Once activated, AMPK exerts its effects through the phosphorylation of multiple downstream targets, leading to the inhibition of biosynthetic pathways, including fatty acid synthesis, cholesterol synthesis, and protein synthesis, all of which are energy-consuming. Conversely, it promotes processes that generate ATP, such as glucose uptake, glycolysis, fatty acid oxidation, and mitochondrial biogenesis. For example, AMPK activation enhances glucose transporter 4 (GLUT4) translocation to the plasma membrane, increasing glucose uptake into cells, and upregulates the expression of genes involved in mitochondrial function and fatty acid oxidation via the activation of transcription factors like PGC-1α. AMPK also plays a significant role in systemic energy balance and has been implicated in the response to hormonal signals, such as leptin and adiponectin. These hormones influence AMPK activity in key metabolic tissues including the liver, skeletal muscle, and adipose tissue, thereby integrating signals from nutrient status and energy expenditure.
AMPK activation is considered beneficial for several metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. It improves insulin sensitivity, enhances glucose uptake, and increases fatty acid oxidation, all of which are beneficial in the management of these conditions. Additionally, AMPK is involved in other cellular processes such as autophagy and cell growth regulation, linking energy status with cell growth, proliferation, and survival.
Figure 1 AMPK structure and activation. (Herzig, 2018)
PRKAA1, also known as AMP-activated protein kinase alpha 1 (AMPKα1), is a catalytic subunit of AMP-activated protein kinase (AMPK), an essential enzyme that plays a crucial role in maintaining cellular energy homeostasis. AMPK functions as a cellular energy sensor, activated by increases in the AMP/ATP ratio which typically occurs during metabolic stress when cellular energy levels are depleted. Once activated, AMPK orchestrates a broad spectrum of biochemical pathways to restore energy balance by enhancing catabolic processes that generate ATP, and by inhibiting anabolic processes that consume ATP. The PRKAA1 subunit is central to the activation and function of the AMPK complex. It is expressed ubiquitously in various tissues, with significant presence in key metabolic organs such as the liver, muscle, and brain. Activation of AMPK via PRKAA1 leads to the phosphorylation and regulation of multiple downstream targets involved in glucose and lipid metabolism, including stimulation of glucose uptake and fatty acid oxidation, and inhibition of cholesterol synthesis, lipogenesis, and gluconeogenesis. Given its pivotal role in energy regulation, PRKAA1 is critically involved in the pathophysiology of metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. Pharmacological activation of AMPK through PRKAA1 has therefore been targeted as a therapeutic strategy for these conditions. AMPK activators, such as metformin, a widely used type 2 diabetes medication, indirectly stimulate AMPK, highlighting the clinical relevance of PRKAA1 in metabolic disease management. Additionally, research into PRKAA1 extends to its role in cancer and neurodegenerative diseases, where its energy-sensing capabilities are crucial for regulating cell growth, proliferation, and survival under metabolic stress conditions.
PRKAB1, also known as AMP-activated protein kinase beta 1, is another regulatory subunit of the AMP-activated protein kinase (AMPK) complex. The PRKAB1 subunit serves multiple roles: it provides structural support to the complex, contributes to the regulation of AMPK activity, and mediates the localization of AMPK to certain cellular compartments. The beta subunit, including PRKAB1, contains a carbohydrate-binding module that allows AMPK to interact with glycogen, thereby linking AMPK activity to cellular energy stores. This interaction is essential for the proper regulation of energy balance within the cell. By sensing and responding to changes in cellular energy status, indicated by fluctuations in the levels of AMP, ATP, and ADP, PRKAB1 plays a crucial role in activating the AMPK complex during energy stress. Functionally, when energy is scarce, AMPK, aided by PRKAB1, activates catabolic pathways that generate ATP, such as glucose uptake and fatty acid oxidation, and suppresses anabolic pathways that consume ATP, including protein and lipid synthesis. This makes PRKAB1 integral to the management of metabolic responses in the body, impacting processes like glucose metabolism, mitochondrial biogenesis, and lipid metabolism. Given its central role in energy metabolism, PRKAB1 is also implicated in several pathological conditions, such as type 2 diabetes, obesity, and cardiovascular diseases. Targeting the AMPK pathway, and by extension PRKAB1, is a therapeutic strategy for treating these metabolic disorders. Furthermore, research into PRKAB1's role extends into areas such as cancer and neurodegenerative diseases, where energy management and metabolic control are disrupted.
PRKAG1, also known as AMP-activated protein kinase gamma 1, is one of the regulatory subunits of AMPK complex. The gamma subunit, including PRKAG1, is primarily responsible for binding adenine nucleotides (AMP, ADP, and ATP), which directly impacts the activity of the AMPK complex. The presence of AMP or ADP promotes the activation of AMPK, while ATP binding inhibits it. This nucleotide-binding feature enables PRKAG1 to regulate the kinase activity of AMPK in response to changes in cellular energy status, activating AMPK when cellular energy is low and deactivating it when energy is plentiful. PRKAG1's function is critical in various physiological processes that require energy regulation, such as glucose and lipid metabolism, muscle activity, and overall energy expenditure. By affecting AMPK activation, PRKAG1 influences pathways that control glucose uptake, fatty acid oxidation, and mitochondrial biogenesis, contributing to the maintenance of energy homeostasis in response to metabolic stresses. Alterations in PRKAG1 function have been associated with various metabolic disorders, including diabetes and obesity, as well as cardiovascular diseases. Because of its central role in managing energy utilization and storage, PRKAG1 is considered a potential therapeutic target for metabolic diseases. Additionally, research into PRKAG1 also extends into its implications in exercise physiology and muscle function, making it a significant focus in studies related to enhancing physical performance and addressing metabolic inefficiencies.
Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
PRKAA1 | AMPK; AMPKa1; AMPK alpha 1 | 5562 | Q13131 | The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. |
PRKAB1 | AMPK; HAMPKb | 5564 | Q9Y478 | The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex. |
PRKAB2 | PRKAB2; protein kinase, AMP-activated, beta 2 non-catalytic subunit; 5-AMP-activated protein kinase subunit beta-2; AMPK beta 2; 5 AMP activated protein kinase beta 2 subunit; 5 AMP activated protein kinase subunit beta 2; AMP activated protein kinase beta 2 non catalytic subunit; AMPK beta 2; AMPK beta 2 chain; AMPK subunit beta 2; MGC61468; PRKAB 2; Protein kinase AMP activated beta 2 non catalytic subunit; AMPK beta-2 chain; OTTHUMP00000015910; AMPK subunit beta-2; 5-AMP-activated protein kinase, beta-2 subunit; | 5565 | O43741 | The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013] |
PRKAG1 | AMPKG | 5571 | P54619 | The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding distinct isoforms have been observed. |
PRKAG3 | AMPKG3; SMGMQTL | 53632 | Q9UGI9 | The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. |
CAT | Product Name | Biomarker | Assay | Image |
ZG-0285F | Mouse Anti-PRKAA1 Recombinant Antibody (ZG-0285F) | PRKAA1 | WB | |
ZG-0286F | Mouse Anti-PRKAB1 Recombinant Antibody (ZG-0286F) | PRKAB1 | WB | |
ZG-0029J | Mouse Anti-PRKAA1 Recombinant Antibody (clone 5G11) | PRKAA1 | WB | |
ZG-0030J | Mouse Anti-PRKAA1 Recombinant Antibody (clone 9G3) | PRKAA1 | IHC | |
VS3-FY1183 | Recombinant Rabbit Anti-PRKAA1 (phospho Ser496) Antibody (clone R01-3B7) | PRKAA1 | WB |
For research use only. Not intended for any clinical use.
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