Extended Data Fig. 2: Glutarate is an inhibitor of αKGDDs.
From: Glutarate regulates T cell metabolism and anti-tumour immunity
a, Illustration of alpha-ketoglutarate (αKG) dependent dioxygenase (αKGDD) reactions investigated in this study. (Adapted from BioRender.com) b, Cell free enzymatic inhibition assay for TET2 using increasing concentrations of DEG. c, qPCR analysis of CD8+ T cells treated with 500 µM DEG for 7 days. Each dot represents one human donor relative to untreated donor control (dotted black line), normalised to HPRT. Two-tailed one sample t-test; GLUT1 n = 8; PDHK1 n = 5; BNIP3 n = 5; CA9 n = 6. d, Log2 FC protein expression of H3K9me2 in human CD8+ T cells treated with +/- 500 µM DEG and 500 µM αKG for 7 days. Ordinary one-way ANOVA; DEG n = 11, αKG n = 3; αKG + DEG n = 3. e, Cell free enzymatic inhibition assay for TET2 using increasing concentrations of glutarate and 5x αKG than in Fig. 2I. Cell free enzymatic assay graphs show Michaelis-Menten line of best fit of at least 3 independent experiments. All scatter plots show median + 95% CI, where each dot represents one donor as indicated.
