Cobalt PeptidesResearch Grade

Scientific Reference

Aicar

Evidence profile: Controlled human evidence

AICAR, also called acadesine, is 5-aminoimidazole-4-carboxamide riboside: a synthetic nucleoside, not a peptide or an amino-acid derivative. Its monophosphate, ZMP, is a natural intermediate in the pathway cells use to build purine nucleotides. AICAR became a standard laboratory tool because cells convert it to ZMP, which mimics AMP and switches on AMP-activated protein kinase (AMPK). A large body of cell and rodent work has used it to study energy sensing, glucose uptake and fatty-acid metabolism. Human clinical work has been limited and has not centred on metabolism. A known weakness of the tool is that ZMP acts on other AMP-sensitive enzymes too, so not every effect attributed to AICAR runs through AMPK.

Mechanism of Action

AICAR enters cells through adenosine transporters and is phosphorylated by adenosine kinase to ZMP. ZMP binds the regulatory gamma subunit of AMPK at sites that normally sense AMP, and this allosteric activation, together with increased phosphorylation of the catalytic alpha subunit, raises the kinase's activity. Activated AMPK phosphorylates targets such as acetyl-CoA carboxylase, shifting cells away from lipid synthesis and toward processes that generate ATP. ZMP accumulates to high concentrations, however, and has been reported to affect other AMP-regulated enzymes, including fructose-1,6-bisphosphatase and glycogen phosphorylase. Studies that need to separate AMPK-dependent effects often pair AICAR with genetic knockout models.

Molecular Information

  • Type: Nucleoside analogue
  • Molecular weight: 258.23 g/mol
  • Molecular formula: C9H14N4O5
  • CAS: 2627-69-2

Published Research

  • Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes

    Mendler M et al. · Acta diabetologica · 2018 · Clinical

    PMID 29546577 — View on PubMed

  • 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men

    Cuthbertson DJ et al. · Diabetes · 2007 · Clinical

    PMID 17513706 — View on PubMed