5'-AMP-activated protein kinase catalytic subunit alpha (AMPK alpha) (AMPKα)

5'-AMP‑activated protein kinase catalytic subunit alpha is the **catalytic core** of the heterotrimeric enzyme complex known as **AMP‑activated protein kinase** (**AMPK**). The α subunit exists as two main isoforms in mammals—PRKAA1 and PRKAA2—and contains a serine/threonine kinase domain responsible for phosphorylating downstream targets involved in energy homeostasis. The full AMPK complex also includes regulatory β and γ subunits with multiple isoforms each. As a central regulator of cellular energy status expressed ubiquitously across eukaryotic cells, **AMPK senses increases in AMP/ADP relative to ATP**, triggering its activation through allosteric mechanisms and phosphorylation at threonine‑172. Once activated, it shifts cell metabolism toward catabolic pathways that generate ATP while inhibiting anabolic processes that consume it—thus restoring energy balance during metabolic stress such as exercise or nutrient deprivation. The α isoforms play non-redundant roles depending on tissue context; for example, specific functions have been described for PRKAA2 in photoreceptor metabolism. Dysregulation or mutation can contribute to diseases including diabetes/metabolic syndrome and cardiovascular disorders due to their pivotal role controlling glucose uptake, lipid oxidation/synthesis, mitochondrial function, autophagy, and more.

Other names

AMP-activated protein kinase catalytic subunit alphaAMPKαPRKAA1 (for isoform 1)PRKAA2 (for isoform 2)Protein kinase AMP-activated catalytic subunit alpha

Drugs targeting this molecule typically act by activating the enzyme to enhance its phosphorylation activity on downstream targets. This leads to increased catabolic processes that generate ATP and decreased anabolic processes that consume ATP. For example, metformin activates AMPK indirectly by increasing the cellular AMP/ATP ratio.