a, Chemical structure of the steroid derivative dehydroepiandosterone (DHEA). b, In vitro activity of DHEA against recombinant human G6PD (mean ± SD, n = 3). c, Western blots of G6PD knockout cells generated using CRISPR-Cas9 (HCT116 knockout is clonal; HepG2 is batch; “ctrl” represents an intergenic control). See Supplementary Figure 16 for uncropped gels. Representative results of 2 independent experiments. d, Assays for G6PD cellular activity: (i) 6-phosphogluconate (6-pg) levels in HepG2 cells, (ii) deuterium (2H, small black circle) incorporation into NADPH (active hydride) and free palmitic acid from [1-2H]-glucose in HCT116 cells. e, f, g, DHEA (100 μM, 2 h) does not phenocopy G6PD knockout (TIC, total ion count by LC-MS) (mean ± SD, n = 3). p value calculated using a two-tailed unpaired Student’s t-test.