Table 1.
The Top 20 Metabolites of 590 Whose Concentrations Are Predicted to Be Altered the Most by DFA as a Result of AGT LoF
| Rank (Differential Flux Balance) | Metabolite Name | KEGG ID | Predicted Change (FVA) |
|---|---|---|---|
| 1 | serine | C00065 | − |
| 2 | alanine | C00041 | = |
| 3 | pyruvate/hydroxypyruvate | C00022/C00168 | − |
| 4 | glyoxylate | C00048 | + |
| 5 | glycine | C00037 | + |
| 6 | glycerate | C00258 | − |
| 7 | glycolate | C00160 | + |
| 8 | glycolaldehyde | C00266 | = |
| 9 | glyceraldehyde | C02154 | − |
| 10 | hypoxanthine | C00262 | + |
| 11 | xanthine | C00385 | = |
| 12 | glutamate | C00217 | − |
| 13 | oxaloacetate | C00036 | + |
| 14 | glutathione | C00051 | = |
| 15 | glutathione disulfide | C00127 | = |
| 16 | histidine | C00135 | = |
| 17 | α-ketoglutarate | C00026 | − |
| 18 | histamine | C00388 | − |
| 19 | thymine | C00178 | = |
| 20 | dihydrothymine | C00906 | = |
Metabolites are ranked by summing up the contribution of all differential fluxes involving each metabolite. The metabolites known to accumulate in the urine of PH1 patients (glyoxylate, glycolate, and oxalate) (Xia and Wishart, 2010) are shown in italic. Oxalate is ranked at position 39 of 590 (Table S3), hence it is not shown in this table. Column 4 reports the predicted sign of change in metabolite concentrations as computed by FVA (Supplemental Experimental Procedures): the metabolite concentration can be elevated (+), reduced (−), or (=) no sign could be predicted by FVA. Small molecules (e.g., water and carbon dioxide), co-factors (e.g., NADP and ATP), and a set of other metabolites were not considered because they are involved in a large number of reactions. The complete list of all metabolites and co-factors is reported in Table S2. Details on the analysis can be found in the Supplemental Experimental Procedures.