Alkamines reveal a hidden layer of steroid and drug metabolism

Agongo, J.; Panga, S. R.; Xing, S.; Charron-Lamoureux, V.; Gouda, H.; El Abiead, Y.; Nelson, M. R.; Patan, A.; Carrillo Terrazas, M.; Kvitne, K. E.; Seo, J. I.; Rajkumar, P.; Giddings, S.; Mannochio-Russo, H.; Zemlin, J.; Mohanty, I.; Sala-Climent, M.; Hu, Z.; Deleray, V.; Yeboah, S.; Zhao, H. N.; Caraballo Rodriguez, A. M.; Williams, C. E.; Williams, C. L.; Goncalves Nunes, W. D.; Dorrestein, K.; Cao, J.; Shepherd, I.; Bock, R.; Roethler, N.; Jinich, A.; Burnett, L. A.; Carver, J.; Devine, R. N.; Arnatt, C. K.; Murray, I. A.; Knight, R.; Guma, M.; Hagey, L. R.; Perdew, G.; Bandeira, N.; Wang,

doi:10.64898/2026.05.13.724743

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bioRxiv · 10.64898/2026.05.13.724743

Alkamines reveal a hidden layer of steroid and drug metabolism

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Abstract

Biomedical research overlooks most genes in favor of a well-studied minority, yet whether analogous blind spots exist in metabolomics remains unknown. We show that reductive amination, forming secondary amines from aldehydes or ketones and amines, generates a previously hidden class of metabolites we term alkamines. Multiplexed synthesis of 8,475 alkamines combined with MS/MS searches across 1.7 billion spectra identified 1,626 candidates across multiple species and organs. Of these, 56 were confirmed in biological samples, including 27 steroid- and 12 drug-derived alkamines matching prescription patterns. Notably, 77% of synthesized alkamines are absent from PubChem. This combinatorial logic likely explains why alkamines have evaded detection and suggests drug metabolism frameworks substantially underestimate drug-derived metabolite diversity. Reductive amination is an overlooked route modifying steroids, bile acids, and xenobiotics.

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Agongo, J., Panga, S. R., Xing, S., Charron-Lamoureux, V., Gouda, H., El Abiead, Y., Nelson, M. R., Patan, A., Carrillo Terrazas, M., Kvitne, K. E., Seo, J. I., Rajkumar, P., Giddings, S., Mannochio-Russo, H., Zemlin, J., Mohanty, I., Sala-Climent, M., Hu, Z., Deleray, V., Yeboah, S., Zhao, H. N., Caraballo Rodriguez, A. M., Williams, C. E., Williams, C. L., Goncalves Nunes, W. D., Dorrestein, K., Cao, J., Shepherd, I., Bock, R., Roethler, N., Jinich, A., Burnett, L. A., Carver, J., Devine, R. N., Arnatt, C. K., Murray, I. A., Knight, R., Guma, M., Hagey, L. R., Perdew, G., Bandeira, N., Wang,. 2026-05-15. Alkamines reveal a hidden layer of steroid and drug metabolism. https://doi.org/10.64898/2026.05.13.724743

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