Table 3.
Altered serum abundance of components of the tryptophan metabolism subpathway in Oat1 KO or Oat3 KO mice
| Metabolites | Oat1 KO fold change | Altered in Oat1 KO serum (p-value) | Existing OAT1 in vitro support (reference) | Oat3 KO fold change | Altered in Oat3 KO serum (p-value) | Existing OAT3 in vitro support (reference) | Signaling role (reference) |
|---|---|---|---|---|---|---|---|
| 3-Indoxyl sulfate | 4.29 | ✓ (0.001) | (35) | 2.88 | ✓ (0.005) | (35, 69) | AhR activator (62) |
| 5-Hydroxyindoleacetate | NM | NM | 1.28 | ||||
| Anthranilate | 2.67 | ✓ (0.000) | (70) | 1.21 | (70) | ||
| C-glycosyltryptophan | 1.51 | ✓ (0.006) | 0.82 | ||||
| Indole-3-carboxylate | 1.20 | 1.88 | |||||
| Indoleacetate | 1.29 | (69) | 2.37 | (69) | AhR activator (71) | ||
| Indoleacetylglycine | 2.59 | ✓ (0.001) | 1.96 | ||||
| Indolelactate | 2.63 | ✓ (0.000) | This paper | 2.37 | ✓ (0.009) | This paper | |
| Indolepropionate | 0.89 | 2.25 | PXR, NF-kB signaling inhibitor (72, 73) | ||||
| Indolepropionylglycine | 1.49 | NM | NM | ||||
| Kynurenate | 2.51 | ✓ (0.000) | (70) | 1.51 | (70) | AhR, GPCR, NMDAR activator (74, 75, 76) | |
| Kynurenine | 1.58 | ✓ (0.006) | (35) | 1.13 | ✓ (0.096) | AhR activator (77) | |
| N-acetylkynurenine | 1.68 | ✓ (0.008) | 2.11 | ✓ (0.041) | Potential AhR activator (78) | ||
| N-acetyltryptophan | 0.97 | 2.68 | ✓ (0.054) | GPCR activator (79) | |||
| N-formylanthranilate | 4.54 | ✓ (0.002) | NM | NM | |||
| Picolinate | 1.51 | (70) | 2.02 | (70) | |||
| Serotonin | 0.92 | 1.75 | ✓ (0.036) | AhR, GPCR activator (80, 81) | |||
| Tryptophan | 0.79 | ✓ (0.001) | 0.87 | ||||
| Xanthurenate | 5.29 | ✓ (0.000) | (35, 70, 82) | 1.17 | (70, 82) | AhR activator (74) |
Of those that are altered, only tryptophan decreased in abundance. ✓ represents statistical significance. The p-values by Welch's t-test are in parentheses. NM is not measured. All altered metabolites below had effect sizes (Cohen's d) between 1.74 and 4.17.