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The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase

Research output: Contribution to journalArticlepeer-review

João M. Ribeiro, María Jesús Costas, Alicia Cabezas, Brigitte Meunier, Alexandros Onoufriadis, José Carlos Cameselle

Original languageEnglish
Pages (from-to)1453-1457
Number of pages5
JournalFEBS Letters
Issue number11
Accepted/In press2022
PublishedJun 2022

Bibliographical note

Funding Information: Previous research in the Grupo de Enzimología in Badajoz was funded by Consejería de Economía e Infraestructuras, Junta de Extremadura, Spain (grant numbers IB16066 and GR18127), cofunded by the European Regional Development Fund. Publisher Copyright: © 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies

King's Authors


TKFC-encoded triokinase catalyses glyceraldehyde phosphorylation in fructose metabolism and favours lipogenesis in mice. In Tkfc knockouts or knockdowns, fructose oxidation predominates over lipogenesis. The highly prevalent human variant Ala185Thr-Triokinase/FMN cyclase (TKFC) has been reported to be ‘null’ for fructose metabolism, since Ala185-TKFC rescues the mouse TKFC-deficient phenotype, whereas Ala185Thr-TKFC does not. Such report implies that most humans would display a noncanonical fructose metabolism, but it ignores the well-characterized triokinase activity of Ala185Thr-TKFC. Here, earlier evidence is summarized, along with new evidence that both human variants are equally active in yeast. Therefore, future research on triokinase in the context of human fructose metabolism should consider that Ala185Thr-TKFC is not biochemically ‘null’.

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