AICAR (50mg)

Description

Note: AICAR does not use Smad signaling or ligand/receptor kinetics like myostatin-related peptides; instead, its biochemical relevance is AMPK activation, mitochondrial biogenesis, and metabolic gene expression. So the highly technical version will focus on AMPK pathway mechanics, second messengers, phosphorylation cascades, and downstream gene targets – the correct scientific domain.

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AICAR – Advanced Biochemical Mechanism & Signaling Profile

AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) is an AMP analog and an established activator of the AMP-activated protein kinase (AMPK) pathway in metabolic research models. Inside cells, AICAR is converted to ZMP (AICA-ribotide), a synthetic analog of AMP. ZMP binds to the γ-subunit of AMPK, promoting allosteric activation and preventing dephosphorylation of the AMPK α-subunit at Thr172, the critical phosphorylation site for AMPK signaling.

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Primary Signaling Pathway: AMPK Activation

Mechanism:

1. AICAR enters cells and is phosphorylated to ZMP

2. ZMP mimics rising AMP levels

3. ZMP binds the regulatory site of AMPK (γ-subunit)

4. AMPK becomes activated through:

   • Allosteric activation

   • Increased phosphorylation by LKB1 and CaMKKβ

   • Decreased dephosphorylation by phosphatases

Resulting signaling cascades studied:

• Inhibition of mTORC1

• Increased fatty-acid oxidation

• Enhanced glucose uptake

• Upregulation of mitochondrial biogenesis and oxidative capacity

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Downstream Gene Targets & Transcription Programs Studied

Activated AMPK influences transcription factors and coactivators including:

✅ PGC-1α – mitochondrial biogenesis and oxidative phosphorylation
✅ SIRT1/SIRT3 coordination with AMPK for mitochondrial remodeling
✅ CPT1 and ACADs – fatty-acid β-oxidation genes
✅ GLUT4 – glucose transporter expression in metabolic models
✅ ACC (acetyl-CoA carboxylase) – phosphorylated and inhibited, reducing malonyl-CoA, enhancing fatty-acid entry into mitochondria
✅ TSC2 & Raptor phosphorylation – suppression of mTORC1 signaling

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Metabolic Pathway Effects (In-Vitro Research Context)

AICAR-mediated AMPK activation has been investigated in:

• Glucose homeostasis models: increased glucose uptake via AS160 phosphorylation and GLUT4 translocation

• Mitochondrial studies: induction of NRF1, NRF2, Tfam expression linked to mitochondrial replication

• Lipid oxidation: upregulation of CPT1 and β-oxidation cycles

• Autophagy research: ULK1 phosphorylation downstream of AMPK and mTOR inhibition

• Energy stress simulations: ZMP accumulation mimics high AMP:ATP ratio without requiring caloric or hypoxic stress

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Second Messengers & Phosphorylation Network

AMPK activation triggers a broad phosphorylation cascade:

• ↑ p-AMPK (Thr172)

• ↓ p-ACC (Ser79) → disinhibits fatty-acid import into mitochondria

• ↑ p-TSC2 / p-Raptor → mTORC1 suppression

• ↑ p-ULK1 → autophagy initiation

• ↑ p-AS160 → GLUT4 translocation

These events make AICAR a powerful research tool in the controlled study of metabolic regulation and mitochondrial biology.

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Research Classification

AICAR is supplied exclusively for laboratory, in-vitro scientific research.
It is not approved for human or animal use, medical treatment, or diagnostic procedures.