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

FEBS Letters

article

João M. Ribeiro¹  María Jesús Costas¹  Alicia Cabezas¹  Brigitte Meunier²  Alexandros Onoufriadis³  José Carlos Cameselle¹ 

[1] Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura;Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell;St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London

关键词: fructose metabolism;    fructose oxidation;    glyceraldehyde crossroads;    glyceraldehyde phosphorylation;    lipogenesis;    rs2260655;    single nucleotide polymorphism;    TKFC;    triokinase and FMN cyclase;   

DOI  :  10.1002/1873-3468.14309

来源: John Wiley & Sons Ltd.

【 摘 要 】

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’.

【 授权许可】

Unknown