Pietzke, M., Burgos-Barragan, G., Wit, N., Tait-Mulder, J., Sumpton, D., Mackay, G. M., Patel, K. J. and Vazquez, A. (2020) Amino acid dependent formaldehyde metabolism in mammals. Communications Chemistry, 3, 78. (doi: 10.1038/s42004-020-0324-z) (PMID:36703413) (PMCID:PMC9814826)
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Abstract
Aldehyde dehydrogenase class 3, encoded by ADH5 in humans, catalyzes the glutathione dependent detoxification of formaldehyde. Here we show that ADH5 deficient cells turn over formaldehyde using alternative pathways starting from the reaction of formaldehyde with free amino acids. When mammalian cells are exposed to formaldehyde, the levels of the reaction products of formaldehyde with the amino acids cysteine and histidine - timonacic and spinacine - are increased. These reactions take place spontaneously and the formation of timonacic is reversible. The levels of timonacic are higher in the plasma of Adh5−/− mice relative to controls and they are further increased upon administration of methanol. We conclude that mammals possess pathways of cysteine and histidine dependent formaldehyde metabolism and that timonacic is a formaldehyde reservoir.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by Cancer Research UK grant A21140 (awarded to AV). The authors would like to thank the Core Services and Advanced Technologies at the Cancer Research UK Beatson Institute (A17196), with particular thanks to the Metabolomics and the Cancer Research UK Glasgow Centre (A18076). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sumpton, Mr David and Mackay, Dr Gillian and Tait-Mulder, Dr Jacqueline and Vazquez, Alexei |
| Authors: | Pietzke, M., Burgos-Barragan, G., Wit, N., Tait-Mulder, J., Sumpton, D., Mackay, G. M., Patel, K. J., and Vazquez, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Communications Chemistry |
| Publisher: | Nature Research |
| ISSN: | 2399-3669 |
| ISSN (Online): | 2399-3669 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Communications Chemistry 3: 78 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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