AMP-activated protein kinase catalytic subunit alpha (AMPK-α) (AMPK-α)

AMP-activated protein kinase catalytic subunit alpha (AMPK-α) is the enzymatic component of the heterotrimeric AMPK complex, which serves as a master regulator of cellular and whole-body energy homeostasis [1, 6]. It functions as a metabolic sensor that is activated in response to energy stress, characterized by an increase in the AMP/ATP or ADP/ATP ratio [4, 10]. Once activated, AMPK-α phosphorylates a wide array of downstream targets to inhibit energy-consuming anabolic processes, such as lipid and protein synthesis, while stimulating energy-producing catabolic pathways like fatty acid oxidation and glucose uptake [8, 14]. This makes it a primary therapeutic target for metabolic disorders, including type 2 diabetes and obesity, where it helps restore insulin sensitivity and glucose balance [3, 12]. Beyond its metabolic roles, AMPK-α is involved in regulating autophagy, cell growth through the inhibition of the mTORC1 pathway, and inflammatory responses [1, 15]. Pharmacological modulation includes indirect activators like metformin and direct small-molecule activators such as MK-8722 [14, 15]. However, therapeutic development faces challenges such as potential cardiac hypertrophy and the complex, context-dependent role of AMPK in cancer progression [15].

Other names

PRKAA1PRKAA25'-AMP-activated protein kinase catalytic subunit alpha-15'-AMP-activated protein kinase catalytic subunit alpha-2ACACA kinaseHMGCR kinaseTau-protein kinase PRKAA1

Activation of the catalytic subunit through allosteric binding of AMP/ADP or direct small-molecule activators, leading to phosphorylation of downstream metabolic and growth-regulating substrates.