Table 2. Pathway enrichment analysis of metformin-suppressed metabolites from MKR mice.
| KEGG pathway name | Overlapping metabolites | All metabolites | Pmetabolites | Qmetabolites |
|---|---|---|---|---|
| Down regulated in MKR (N = 82) | ||||
| Glycine, serine and threonine metabolism | 11 | 50 | 2.10E-09 | 6.57E-08 |
| Arginine and proline metabolism | 11 | 91 | 1.37E-06 | 2.32E-05 |
| Purine metabolism | 10 | 92 | 1.14E-05 | 0.000178 |
| Cysteine and methionine metabolism | 7 | 57 | 0.000118 | 0.00152 |
| Alanine, aspartate and glutamate metabolism | 5 | 28 | 0.000196 | 0.00226 |
| Taurine and hypotaurine metabolism | 4 | 22 | 0.000832 | 0.00736 |
| Nicotinate and nicotinamide metabolism | 5 | 49 | 0.00273 | 0.0186 |
| Down regulated by metformin (N = 125) | ||||
| Alanine, aspartate and glutamate metabolism | 13 | 28 | 2.74E-13 | 1.60E-11 |
| Glyoxylate and dicarboxylate metabolism | 14 | 58 | 9.65E-10 | 2.17E-08 |
| Arginine and proline metabolism | 17 | 91 | 1.01E-09 | 2.22E-08 |
| Glycine, serine and threonine metabolism | 13 | 50 | 1.47E-09 | 3.10E-08 |
| Histidine metabolism | 11 | 45 | 5.85E-08 | 1.08E-06 |
| Cysteine and methionine metabolism | 11 | 57 | 7.79E-07 | 1.08E-05 |
| Citrate cycle (TCA cycle) | 7 | 20 | 1.17E-06 | 1.52E-05 |
| Taurine and hypotaurine metabolism | 7 | 22 | 2.44E-06 | 3.06E-05 |
| Pentose phosphate pathway | 8 | 35 | 7.13E-06 | 7.58E-05 |
| Nicotinate and nicotinamide metabolism | 9 | 49 | 1.27E-05 | 0.000116 |
| Glutathione metabolism | 8 | 38 | 1.37E-05 | 0.000125 |
| Butanoate metabolism | 8 | 41 | 2.48E-05 | 0.000215 |
| Oxidative phosphorylation | 5 | 16 | 8.18E-05 | 0.000632 |
| Glycerophospholipid metabolism | 8 | 52 | 0.000147 | 0.00105 |
| Sulfur metabolism | 6 | 29 | 0.000192 | 0.00133 |
| Choline metabolism in cancer | 4 | 11 | 0.000232 | 0.0015 |
| D-Glutamine and D-glutamate metabolism | 4 | 12 | 0.00034 | 0.00214 |
| Purine metabolism | 10 | 92 | 0.000426 | 0.0026 |
| Valine, leucine and isoleucine biosynthesis | 5 | 23 | 0.000531 | 0.00315 |
| Pyrimidine metabolism | 8 | 66 | 0.000786 | 0.00449 |
| Thiamine metabolism | 5 | 30 | 0.00189 | 0.00987 |
The KEGG IDs of metabolites that lie >0.05 unit away from y = -x in Fig 2B were used as high-confidence metabolites specific to MKR for pathway enrichment analyses with IMPaLA. Similarly, the KEGG IDS of metabolites that lie > 0.05 unit away from y = x in Fig 2B were scored as high-confidence metabolites specific to metformin treatment in MKR for IMPaLA analyses. The Q-value cut-off were < 0.01 (except for “Nicotinate and nicotinamide metabolism” that is included for comparison purpose). No enrichment was found for both upregulated metabolite groups in MKR (N = 42) and in metformin treatment (N = 17). The pathways that found in both groups are in italics for the metformin-treatment group.