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5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPKα1 (also written as AMPK alpha 1 or PRKAA1))

Target
AMPKα1 (also written as AMPK alpha 1 or PRKAA1)
Molecular classification
Enzyme (Serine/threonine protein kinase), Energy sensor protein kinase
01

Overview

5'-AMP–activated protein kinase catalytic subunit alpha‑1 is the main catalytic component of the heterotrimeric AMPK complex. Encoded by the PRKAA1 gene, it belongs to the serine/threonine protein kinase family. As part of AMPK, it acts as a central regulator (“energy sensor”) that maintains cellular energy homeostasis. When activated by increased intracellular AMP/ATP ratios—such as during metabolic stress—it phosphorylates key enzymes and transcription factors involved in glucose uptake, fatty acid oxidation, autophagy induction, and inhibition of biosynthetic pathways. Its activity protects cells from ATP depletion by downregulating anabolic processes while upregulating catabolic ones. Dysregulation or altered expression has been linked with cancer progression/metastasis, obesity-related disorders, neurodegeneration via impaired mitophagy/autophagy signaling pathways, and cardiovascular disease risk[1][2][3].

Other names
AMPK alpha 1PRKAA1Protein kinase, AMP-activated, alpha 1AMP-activated protein kinase catalytic subunit alpha 1
02

Mechanism of action

Drugs targeting this molecule typically: - Activate the enzyme by allosteric modulation or by mimicking increased intracellular AMP levels. - Induce phosphorylation events that switch off ATP-consuming biosynthetic pathways and activate catabolic processes to restore energy balance[2].

03

Biological functions

Regulation of cellular energy metabolismSignal transduction in response to changes in the AMP/ATP ratioPhosphorylation of metabolic enzymes and transcription regulators (e.g., CRTC2/TORC2, FOXO3)Regulation of autophagy and cell survival under metabolic stress
04

Disease associations

Cancer (notably implicated in pancreatic cancer metastasis)Metabolic disorders (e.g., obesity, diabetes)Neurodegenerative diseases (via effects on mitophagy and neuronal metabolism)Cardiovascular disease
05

Safety considerations

Overactivation leading to excessive inhibition of anabolic processes.Possible impact on normal tissue homeostasis due to broad role in metabolism.Therapeutic challenges involve achieving tissue-specific activation without systemic side effects.
06

Interacting drugs

A769662

2 more in the full profile.

07

Biomarkers

Phosphorylation status of AMPKα at specific residues can serve as a biomarker for pathway activation.Downstream targets such as phosphorylated ACC may also be used.

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