Table 4.
Altered serum abundance of components of the tryptophan metabolism subpathway in probenecid-treated humans
| Metabolite | Fold change | p value | Significantly altered in humans | Significantly altered in Oat1 KO | Significantly altered in Oat3 KO |
|---|---|---|---|---|---|
| 3-Indoxyl sulfate | 2.44 | 0.0000 | ✓ | ✓ | ✓ |
| 5-Hydroxyindole sulfate | 3.8 | 0.0000 | ✓ | NM | NM |
| 5-Hydroxyindoleacetate | 2.28 | 0.0199 | ✓ | NM | |
| 6-Bromotryptophan | 0.92 | 0.1104 | NM | NM | |
| 8-Methoxykynurenate | 2.76 | 0.0000 | ✓ | NM | NM |
| C-glycosyltryptophan | 0.89 | 0.0138 | ✓ | ✓ | |
| Indole-3-carboxylate | 1.08 | 0.9409 | |||
| Indoleacetate | 1.45 | 0.0019 | ✓ | ||
| Indoleacetoylcarnitine | 0.94 | 0.2267 | NM | NM | |
| Indoleacetylglutamine | 4.35 | 0.0000 | ✓ | NM | NM |
| Indolelactate | 1.29 | 0.0004 | ✓ | ✓ | ✓ |
| Indolepropionate | 1.27 | 0.1012 | |||
| Kynurenate | 2.53 | 0.0000 | ✓ | ✓ | |
| Kynurenine | 1.32 | 0.0001 | ✓ | ✓ | ✓ |
| N-acetylkynurenine (2) | 2.57 | 0.0000 | ✓ | ✓ | ✓ |
| N-acetyltryptophan | 1.72 | 0.0002 | ✓ | ✓ | |
| N-formylanthranilate | 2.05 | 0.0000 | ✓ | ✓ | NM |
| Picolinate | 1.18 | 0.0999 | ✓ | ||
| Serotonin | 1.19 | 0.6392 | ✓ | ||
| Tryptophan | 0.82 | 0.0004 | ✓ | ✓ | |
| Tryptophan betaine | 19.09 | 0.9247 | NM | NM | |
| Xanthurenate | 2.72 | 0.0000 | ✓ | ✓ |
Many of the changes observed in the knockout mice are reflected in the humans treated with probenecid. ✓ represents statistical significance. NM is not measured.