Table 2.
List of significantly altered metabolites due to treatment by a pyrazoleamide drug.
| Main pathway | Subordinate pathway | Metabolite | FCIDC (SD)† | |
|---|---|---|---|---|
| CTL | PYZ | |||
| Amino acid | Creatine metabolism | Creatinine | 0.59 (0.05) | 5.73 (0.32)* |
| Guanidino and acetamido metabolism | 4-Guanidinobutanoate | 1.27 (0.07) | 0.40 (0.03) | |
| Histidine metabolism | Imidazole lactate | 0.71 (0.04) | 3.28 (0.47) | |
| Phenylalanine metabolism | Hippurate | 1.45 (0.11)§ | 3.50 (0.30)*,§ | |
| Carbohydrate | Glycolysis | Lactate | 1.23 (0.14) | 2.12 (0.20) |
| Pentose phosphate pathway | Sedoheptulose-7-phosphate | 0.70 (0.15) | 0.20 (0.03) | |
| Energy | Tricarboxylic acid cycle | α-Ketoglutarate | 1.90 (0.21) | 0.48 (0.05) |
| Citrate | 1.51 (0.20) | 2.25 (0.24) | ||
| Fumarate | 1.69 (0.18)§ | 3.40 (0.35)§ | ||
| Malate | 1.47 (0.15)§ | 3.33 (0.26)*,§ | ||
| Lipid | Fatty acid metabolism | 4-Deoxythreonate | 0.39 (0.05) | 11.40 (1.06) |
| Hexanoylcarnitine | 1.16 (0.09) | 0.44 (0.05) | ||
| Pentadecanoylcarnitine‡ | 0.89 (0.04) | 0.42 (0.02) | ||
| Phosphatidylserine | 1-Palmitoyl-2-oleoyl-GPS (16:0/18:1) | 1.42 (0.08) | 2.08 (0.27) | |
| Sphingolipid synthesis | Sphinganine-1-phosphate | 1.18 (0.07) | 2.39 (0.18) | |
| Nucleotide | Pyrimidine metabolism | Uridine | 1.00 (0.14) | 2.60 (0.45) |
| Peptide | γ-Glutamyl amino acid | γ-Glutamylisoleucine‡ | 1.00 (0.08) | 0.30 (0.03) |
| γ-Glutamylleucine | 1.17 (0.08) | 0.28 (0.02) | ||
CTL uRBC and iRBC cultures maintained in pure RPMI medium, IDC intraerythrocytic developmental cycle, iRBC parasite-infected RBC, GPS glycerophosphoserine, PYZ uRBC and iRBC cultures maintained in RPMI medium with a sublethal dose of a pyrazoleamide drug, RBC red blood cell, RPMI Roswell Park Memorial Institute, SD standard deviation, uRBC uninfected RBC.
†Fold-change (FCIDC) values based on a comparison of the average normalized abundance of a metabolite during the IDC in the iRBC culture relative to that in the uRBC culture. The standard deviation (SD) represents deviation from the mean of 10,000 bootstrap samples (see “Materials and methods”) ‡Metabolite identified based on m/z ratio alone with no external standard for validation. *The temporal variation in metabolite abundance is statistically different (p < 0.001) than the variation reported in uRBC cultures in Ref.22. §Tewari et al.22 found that this metabolite’s abundance changed minimally in uRBC cultures over a 2-day period.