Supplementary Figure 4: Inhibition of QPRT disrupts oxidative phosphorylation and cellular metabolism.

a–e, HuMDMs were treated with vehicle or the QPRT inhibitor phthalic acid (PTH; 500 μM, 20 h). a, LC/MS of NAD⁺ with PTH treatment; n = 3 biologically independent samples per group, shown as mean ± S.E.; **P = 0.0048 by Student’s two-tailed t test. b, Representative trace of PTH-treated huMDMs. c, Basal respiration, maximal respiration, and spare respiratory capacity in PTH-treated huMDMs; n = 4 biologically independent samples per group, shown as mean ± S.E; Basal respiration: **P = 0.0023; maximal respiration **P = 0.0019; spare respiratory capacity: **P = 0.0089; all by Student’s two-tailed t test. d, ECAR in PTH-treated huMDMs; n = 3 biologically independent samples per group, *P < 0.05. e, Hierarchical clustering of targeted metabolomics for glycolysis, pentose phosphate pathway, and citric acid cycle metabolites of huMDMs treated with PTH (500 μM, 20 h; n = 3 biologically independent samples per group). f, Targeted metabolomics from e with PTH-treated huMDMs reveals an upregulation of lactate, the pentose phosphate pathway and proinflammatory TCA intermediates (in red), similar to changes seen in Qprt^–/– macrophages. g, Metabolism of ¹³C[TRP] to NAD⁺ yields M+6–labeled NAD⁺.