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5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) (AMPK alpha-1)

Target
AMPK alpha-1
Molecular classification
Enzyme, Serine/threonine-protein kinase, AMP-activated protein kinase (AMPK) family
01

Overview

5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) is the primary catalytic component of the AMPK complex, a central energy sensor in eukaryotic cells (UniProt: Q13131). It is activated under conditions of metabolic stress, such as hypoxia or glucose deprivation, which increase the cellular AMP:ATP ratio (NCBI Gene: 5562). Upon activation, PRKAA1 phosphorylates a wide array of downstream targets to stimulate catabolic pathways like fatty acid oxidation and glucose transport while inhibiting anabolic processes such as lipid and protein synthesis (PubMed: 29107506). This makes it a critical target for treating metabolic diseases, including type 2 diabetes and obesity, where it helps restore energy balance and improve insulin sensitivity. Additionally, PRKAA1 is involved in regulating cell growth, autophagy, and inflammation, suggesting potential therapeutic applications in oncology and cardiovascular medicine. While indirect activators like metformin are widely used, the development of direct PRKAA1 activators remains an active area of drug discovery aimed at achieving more potent and specific metabolic control (PubMed: 27501152).

Other names
PRKAA1AMPK alpha-1AMPK1AMPKa1Protein kinase AMP-activated catalytic subunit alpha 1
02

Mechanism of action

Activation of the AMPK complex to restore energy balance by promoting catabolic pathways and inhibiting anabolic pathways (PubMed: 29107506).

03

Biological functions

Energy homeostasisGlucose metabolismLipid metabolismAutophagyCell growth regulation
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Disease associations

Type 2 diabetesObesityMetabolic syndromeCancerCardiovascular disease
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Safety considerations

Potential for cardiac hypertrophy (PubMed: 27501152)Gastrointestinal distressHypoglycemia riskPotential tumor promotion in specific contexts
06

Interacting drugs

Metformin

5 more in the full profile.

07

Biomarkers

Phospho-AMPK (Thr172)Phospho-Acetyl-CoA Carboxylase (pACC)

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