Biomedicines · 13 authors, 11 centres
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Using stable isotope-assisted metabolomics in human cancer cell lines, the authors identify a novel pathway in which pentose phosphate pathway intermediate erythrose 4-phosphate is dephosphorylated to erythrose and then oxidized to erythronate by ALDH1A1. Significantly higher erythronate concentrations were measured in lung tumor tissues compared to adjacent normal tissues from patients.
The study employed stable isotope-assisted untargeted metabolomics to identify erythronate as a metabolite accumulating in multiple human cancer cell lines. Stable isotopic tracer experiments demonstrated that erythronate is derived from the third to sixth carbons of glucose, consistent with the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) as the precursor. Chemical inhibitors and genetic silencing confirmed E4P as the starting substrate. Enzyme assay-coupled protein fractionation and proteomics identified ALDH1A1 as the predominant enzyme catalyzing erythrose oxidation to erythronate, and modulating ALDH1A1 expression in cancer cell lines provided supporting evidence. The authors describe a pathway involving dephosphorylation of E4P to erythrose followed by ALDH1A1-mediated oxidation. Elevated erythronate was measured in lung tumor tissues relative to adjacent normal tissues from patients.
