Study summary · research use only
Identification of yeast and human 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAr) transporters
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study, the authors isolated and characterized yeast mutants hypersensitive to AICAr (5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside), the precursor of the monophosphate AICAR. The abstract reports that the thiamine transporters Thi7 and Thi72 can take up AICAr efficiently when overexpressed, and that under standard growth conditions the nicotinamide riboside carrier Nrt1 is the major AICAr transporter in yeast. A study of AICAR accumulation in human cells revealed substantial disparities among cell lines and indicated AICAr enters human cells via purine nucleoside transporters. The authors note significant differences between yeast and human cells in AICAr uptake and AICAR accumulation.
Abstract
5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAr) is the precursor of the active monophosphate form (AICAR), a small molecule with potent anti-proliferative and low energy mimetic properties. The molecular bases for AICAR toxicity at the cellular level are poorly understood. Here, we report the isolation and characterization of several yeast AICAr-hypersensitive mutants. Identification of the cognate genes allowed us to establish that thiamine transporters Thi7 and Thi72 can efficiently take up AICAr under conditions where they are overexpressed. We establish that, under standard growth conditions, Nrt1, the nicotinamide riboside carrier, is the major AICAr transporter in yeast. A study of AICAR accumulation in human cells revealed substantial disparities among cell lines and confirmed that AICAr enters cells via purine nucleoside transporters. Together, our results point to significant differences between yeast and human cells for both AICAr uptake and AICAR accumulation.
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