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

João M Ribeiro , María Jesús Costas , Alicia Cabezas , Brigitte Meunier (1) , Alexandros Onoufriadis , José Carlos Cameselle

1 I2BC - Institut de Biologie Intégrative de la Cellule

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'.

Mots clés: fructose metabolism; glyceraldehyde phosphorylation; TKFC; triokinase and FMN cyclase

Domaines: Sciences du Vivant [q-bio]

João M Ribeiro, María Jesús Costas, Alicia Cabezas, Brigitte Meunier, Alexandros Onoufriadis, et al.. The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase. FEBS Letters, 2022, ⟨10.1002/1873-3468.14309⟩. ⟨hal-03564461⟩