Human aldo-keto reductase family 1 member C3 (AKR1C3) is a steroidogenic and phase I enzyme which is also implicated in breast and prostate cancers, leukemia, and metabolic diseases. Despite this clinical significance, the detailed endogenous biochemical roles of AKR1C3 remain partially defined. Using untargeted metabolomics and tandem MS analysis, we identified a new transformation mediated by AKR1C3, which involves oxidized polyamines. The chemical characterization of the enzymatic product by chemical synthesis revealed a new polyamine metabolite with hydroxyl functionality, which we termed sperminol. We further illustrated that sperminol can activate autophagy <i>in vitro</i> while its precursor, mono-oxidized spermine is upregulated in M1 macrophages. Our metabolomics studies revealed a detoxification role of AKR1C3 in a polyamine pathway and highlighted the functional significance of the new human metabolite, sperminol.

Characterization of a new polyamine transformation catalyzed by human aldo-keto reductase 1C3

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