Abstract
SummaryCordycepin (3′-deoxyadenosine) is a major bioactive agent in Cordyceps militaris, a fungus used in traditional Chinese medicine. It has been proposed to have many beneficial metabolic effects by activating AMP-activated protein kinase (AMPK), but the mechanism of activation remained uncertain. We report that cordycepin enters cells via adenosine transporters and is converted by cellular metabolism into mono-, di-, and triphosphates, which at high cordycepin concentrations can almost replace cellular adenine nucleotides. AMPK activation by cordycepin in intact cells correlates with the content of cordycepin monophosphate and not other cordycepin or adenine nucleotides. Genetic knockout of AMPK sensitizes cells to the cytotoxic effects of cordycepin. In cell-free assays, cordycepin monophosphate mimics all three effects of AMP on AMPK, while activation in cells is blocked by a γ-subunit mutation that prevents activation by AMP. Thus, cordycepin is a pro-drug that activates AMPK by being converted by cellular metabolism into the AMP analog cordycepin monophosphate.
Highlights
Cordycepin (30-deoxyadenosine) is an adenosine analog derived from Cordyceps militaris, a parasitic fungus that infects insect larvae and is highly prized in traditional Chinese medicine (Tuli et al, 2013)
To confirm that the cordycepin 50-monophosphate (CoMP) effect required binding to the crucial CBS3 site on the g subunit, we examined the activation of AMPK complexes in HepG2 cells containing transfected g2 subunits, with either the WT sequence or the R531G mutation
It was shown many years ago that cordycepin is converted inside cells into mono, di, and triphosphates (Klenow, 1963), we have quantified by liquid chromatography-mass spectrometry (LC-MS) the appearance of CoMP, cordycepin diphosphate (CoDP), and cordycepin triphosphate (CoTP) and the disappearance of AMP, ADP, and ATP, as functions of cordycepin concentration and time
Summary
Cordycepin (30-deoxyadenosine) is an adenosine analog derived from Cordyceps militaris, a parasitic fungus that infects insect larvae and is highly prized in traditional Chinese medicine (Tuli et al, 2013). Cordycepin is taken up into cells and converted to mono-, di-, and triphosphates (Klenow, 1963); since it lacks a 30-hydroxyl group, if incorporated into RNA it would cause chain termination. Cordycepin reduces the amount of poly(A)+ RNA without affecting rRNA or tRNA, while mutations in the poly(A) polymerase Pap have similar effects on global gene expression (Holbein et al, 2009). Cordycepin reduces the poly(A) tail lengths of some, but not all, mRNAs (Wong et al, 2010). These results indicate that a major mode of cordycepin action is to inhibit 30 end processing of mRNAs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
