Protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1)

Protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), commonly known as AMPK alpha 1, is the catalytic component of the heterotrimeric AMP-activated protein kinase (AMPK) complex (UniProt: Q13131). It acts as a master regulator of cellular energy homeostasis by sensing changes in the AMP:ATP ratio, becoming activated when energy levels are low (Hardie et al., 2012, Nature Reviews Molecular Cell Biology). Upon activation, PRKAA1 phosphorylates key metabolic enzymes to promote glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while suppressing lipid synthesis and gluconeogenesis (Zhang et al., 2017, Cell Metabolism). This makes it a primary therapeutic target for metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. In addition to metabolism, PRKAA1 influences cell growth and autophagy through the inhibition of the mTOR pathway. While many drugs like metformin activate AMPK indirectly, newer small molecules target the alpha subunit directly to achieve more potent and specific metabolic effects (PubChem CID 4091). However, therapeutic development faces challenges such as potential cardiac side effects associated with systemic AMPK activation. The inclusion of mRNA in the target name is likely a mis-specification, as the functional therapeutic target is the protein product.

Other names

AMPK alpha 1AMPK1AMP-activated protein kinase catalytic subunit alpha-1AMPKa1ACACAD

Direct or indirect activation of the AMPK complex to stimulate ATP-producing pathways and inhibit ATP-consuming pathways via phosphorylation of downstream targets like ACC and TSC2.