PRKAG1

PRKAG1 encodes the regulatory gamma-1 subunit of AMP-activated protein kinase (AMPK). AMPK is a heterotrimeric enzyme complex that plays a crucial role in cellular energy homeostasis. It is activated by increases in the AMP/ATP ratio, indicating a state of energy depletion. Upon activation, AMPK phosphorylates a variety of downstream targets, leading to increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis, while inhibiting ATP-consuming processes such as protein synthesis and cell growth.

The gamma subunit, including PRKAG1, is responsible for sensing cellular energy levels by binding to AMP, ADP, and ATP. Different gamma subunit isoforms exist (gamma-1, gamma-2, and gamma-3), each encoded by a different gene (PRKAG1, PRKAG2, and PRKAG3, respectively). These isoforms exhibit tissue-specific expression patterns, influencing the regulation of AMPK activity in different tissues. PRKAG1 is predominantly expressed in skeletal muscle, liver, and heart.

Mutations in PRKAG1 have been associated with several conditions. For example, certain mutations in PRKAG1 can cause glycogen storage disease due to impaired AMPK regulation of glycogen metabolism. Furthermore, PRKAG1 variants have been implicated in altered cardiac function and potentially contribute to cardiac hypertrophy. Research continues to explore the precise role of PRKAG1 in various physiological and pathological processes.