Table 1.
Representative fold changes of serum metabolites in male and female homozygous ARE-Del mice compared to wild-type mice. Significant fold changes are marked by red and green colors (p<0.05). All KO; combined male and female homozygous ARE-Del mice (n=12) vs control littermates (n=12), KO F; female homozygous ARE-Del mice (n=6) vs control littermates (n=6), KO M; male homozygous ARE-Del mice (n=6) vs control littermates (n=6).
| SUPER PATHWAY | SUB PATHWAY | BIOCHEMICAL | ALL KO / | KO F / | KO M / |
|---|---|---|---|---|---|
| Amino acid | Alanine and aspartate metabolism | 3-ureidopropionate | 1.12 | 1.11 | 1.13 |
| Butanoate metabolism | 2-aminobutyrate | 0.89 | 0.77 | 1.08 | |
| Cysteine, methionine, SAM, taurine metabolism | 2-hydroxybutyrate (AHB) | 0.85 | 0.77 | 0.99 | |
| methionine | 1.48 | 1.85 | 1.20 | ||
| N-acetylmethionine | 1.41 | 1.64 | 1.20 | ||
| glutamine | 0.85 | 0.88 | 0.81 | ||
| Glutamate metabolism | N-acetylglutamine | 0.77 | 0.98 | 0.64 | |
| beta-hydroxypyruvate | 0.86 | 1.22 | 0.61 | ||
| Glycine, serine and threonine metabolism | betaine | 0.95 | 0.88 | 1.03 | |
| glycine | 1.10 | 1.09 | 1.11 | ||
| N-acetylglycine | 0.68 | 0.47 | 0.95 | ||
| Guanidino and acetamido metabolism | 4-guanidinobutanoate | 1.46 | 1.67 | 1.28 | |
| Histidine metabolism | histidine | 0.89 | 0.97 | 0.82 | |
| urocanate | 0.69 | 0.54 | 1.01 | ||
| Lysine metabolism | lysine | 0.76 | 0.73 | 0.79 | |
| N6-acetyllysine | 1.23 | 1.30 | 1.16 | ||
| pipecolate | 0.88 | 1.06 | 0.76 | ||
| Phenylalanine & tyrosine metabolism | 3-(4-hydroxyphenyl)lactate | 1.37 | 1.44 | 1.27 | |
| 4-hydroxyphenylpyruvate | 1.49 | 1.75 | 1.21 | ||
| N-acetylphenylalanine | 1.32 | 1.55 | 1.06 | ||
| N-acetyltyrosine | 1.38 | 1.84 | 0.99 | ||
| p-cresol sulfate | 0.25 | 0.41 | 0.08 | ||
| phenylalanine | 1.07 | 1.20 | 0.95 | ||
| phenyllactate (PLA) | 1.71 | 1.83 | 1.60 | ||
| tyrosine | 1.20 | 1.39 | 1.03 | ||
| Polyamine metabolism | 5-methylthioadenosine (MTA) | 1.31 | 1.33 | 1.29 | |
| Tryptophan metabolism | 3-indoxyl sulfate | 1.07 | 1.09 | 1.04 | |
| indolelactate | 1.39 | 1.41 | 1.36 | ||
| kynurenine | 3.31 | 2.55 | 5.07 | ||
| N-acetyltryptophan | 0.78 | 0.91 | 0.62 | ||
| serotonin (5HT) | 0.55 | 0.44 | 0.71 | ||
| tryptophan | 0.78 | 0.80 | 0.75 | ||
| Urea cycle; arginine-, proline-, metabolism | citrulline | 1.29 | 1.35 | 1.23 | |
| dimethylglycine | 1.27 | 1.22 | 1.35 | ||
| homocitrulline | 1.52 | 1.22 | 1.88 | ||
| homostachydrine* | 0.81 | 0.79 | 0.82 | ||
| proline | 1.50 | 1.73 | 1.30 | ||
| urea | 1.29 | 1.54 | 1.08 | ||
| Valine, leucine and isoleucine metabolism | 2-hydroxy-3-methylvalerate | 0.96 | 1.30 | 0.83 | |
| 2-methylbutyroylcarnitine | 1.34 | 1.23 | 1.47 | ||
| 3-methyl-2-oxobutyrate | 0.74 | 0.69 | 0.80 | ||
| 3-methyl-2-oxovalerate | 0.61 | 0.57 | 0.65 | ||
| 4-methyl-2-oxopentanoate | 0.62 | 0.63 | 0.61 | ||
| alpha-hydroxyisovalerate | 0.99 | 1.31 | 0.90 | ||
| butyrylcarnitine | 1.46 | 1.57 | 1.31 | ||
| hydroxyisovaleroyl carnitine | 1.20 | 1.18 | 1.24 | ||
| isobutyrylcarnitine | 1.97 | 2.33 | 1.66 | ||
| isoleucine | 0.87 | 0.92 | 0.81 | ||
| isovalerylcarnitine | 1.62 | 1.89 | 1.35 | ||
| propionylcarnitine | 1.74 | 2.11 | 1.42 | ||
| Aminosugars metabolism | erythronate* | 1.16 | 1.27 | 1.07 | |
| Peptide | DiPeptide | alanylalanine | 0.71 | 0.80 | 0.66 |
| gamma-glutamylvaline | 0.95 | 1.03 | 0.90 | ||
| Dipeptide derivative | anserine | 1.53 | 1.77 | 1.42 | |
| g-glutamyl | gamma-glutamylglutamate | 1.39 | 1.17 | 1.60 | |
| gamma-glutamylmethionine* | 1.66 | 1.93 | 1.49 | ||
| gamma-glutamylphenylalanine | 1.54 | 1.64 | 1.45 | ||
| gamma-glutamylthreonine* | 1.14 | 1.12 | 1.16 | ||
| gamma-glutamyltryptophan | 1.31 | 1.21 | 1.45 | ||
| gamma-glutamyltyrosine | 1.58 | 1.65 | 1.52 | ||
| Nucleotide | Purine metabolism, (hypo)xanthine/inosine containing | inosine | 0.32 | 0.52 | 0.28 |
| Purine metabolism, adenine containing | 1-methyladenosine | 0.98 | 0.93 | 1.05 | |
| adenosine | 0.36 | 0.20 | 0.37 | ||
| adenosine 5’-monophosphate (AMP) | 0.39 | 0.96 | 0.38 | ||
| Purine metabolism, guanine containing | guanosine | 0.99 | 1.00 | 0.99 | |
| guanosine 5’- monophosphate (GMP) | 0.86 | 1.00 | 0.84 | ||
| Purine metabolism, urate metabolism | allantoin | 1.23 | 1.25 | 1.22 | |
| urate | 1.33 | 1.26 | 1.40 | ||
| Pyrimidine metabolism, cytidine containing | 2’-deoxycytidine | 1.43 | 1.39 | 1.48 | |
| cytidine | 0.67 | 0.67 | 0.67 | ||
| Pyrimidine metabolism, thymine containing | thymidine | 1.44 | 1.42 | 1.48 | |
| Pyrimidine metabolism, uracil containing | 5,6-dihydrouracil | 1.72 | 2.28 | 1.33 | |
| pseudouridine | 1.25 | 1.17 | 1.35 | ||
| uridine | 0.55 | 0.59 | 0.52 | ||
| Carbohydrate | Fructose, mannose, galactose, starch, and sucrose metabolism | fructose | 0.82 | 0.72 | 0.92 |
| mannose | 0.72 | 0.66 | 0.79 | ||
| Glycolysis, gluconeogenesis, pyruvate metabolism | 1,5-anhydroglucitol (1,5-AG) | 0.56 | 0.61 | 0.52 | |
| glucose | 0.82 | 0.86 | 0.79 | ||
| glycerate | 1.33 | 1.08 | 1.58 | ||
| Nucleotide sugars, pentose metabolism | arabitol | 1.24 | 1.20 | 1.27 | |
| ribitol | 1.49 | 1.75 | 1.25 | ||
| ribulose | 1.75 | 2.40 | 0.89 | ||
| Lipid | Bile acid metabolism | 12-dehydrocholate | 2.84 | 2.15 | 5.60 |
| beta-muricholate | 2.81 | 2.52 | 3.80 | ||
| cholate | 19.28 | 17.52 | 26.94 | ||
| deoxycholate | 5.06 | 4.46 | 5.89 | ||
| tauro-beta-muricholate | 30.85 | 36.17 | 12.80 | ||
| taurochenodeoxycholate | 35.96 | 45.42 | 15.23 | ||
| taurocholate | 28.37 | 32.98 | 17.20 | ||
| taurodeoxycholate | 11.80 | 13.31 | 8.39 | ||
| Carnitine metabolism | 3-dehydrocarnitine* | 1.09 | 1.04 | 1.17 | |
| acetylcarnitine | 0.90 | 0.80 | 1.04 | ||
| carnitine | 0.92 | 0.88 | 0.96 | ||
| deoxycarnitine | 1.12 | 1.07 | 1.20 | ||
| hexanoylcarnitine | 0.95 | 0.72 | 1.41 | ||
| oleoylcarnitine | 1.05 | 0.98 | 1.28 | ||
| Essential fatty acid | dihomo-linolenate (20:3n3 or n6) | 0.69 | 0.80 | 0.63 | |
| docosahexaenoate (DHA; 22:6n3) | 0.74 | 0.69 | 0.80 | ||
| docosapentaenoate (n3 DPA; 22:5n3) | 0.54 | 0.57 | 0.50 | ||
| eicosapentaenoate (EPA; 20:5n3) | 0.78 | 0.89 | 0.68 | ||
| linolenate [alpha or gamma; (18:3n3 or 6)] | 0.75 | 0.70 | 0.80 | ||
| Fatty acid, beta-oxidation | hexanoylglycine | 0.54 | 0.19 | 0.98 | |
| Fatty acid, dicarboxylate | adipate | 0.89 | 1.05 | 0.79 | |
| azelate (nonanedioate) | 0.89 | 0.86 | 0.91 | ||
| sebacate (decanedioate) | 0.90 | 0.87 | 0.93 | ||
| suberate (octanedioate) | 1.02 | 1.01 | 1.02 | ||
| undecanedioate | 0.92 | 0.89 | 0.94 | ||
| Fatty acid, methyl ester | methyl palmitate | 0.99 | 0.96 | 1.01 | |
| Glycerolipid metabolism | glycerol | 0.77 | 0.71 | 0.83 | |
| glycerophosphorylcholine (GPC) | 0.78 | 0.78 | 0.78 | ||
| Inositol metabolism | inositol 1-phosphate (I1P) | 0.79 | 0.90 | 0.72 | |
| myo-inositol | 1.12 | 1.18 | 1.07 | ||
| Ketone bodies | 3-hydroxybutyrate (BHBA) | 0.24 | 0.16 | 0.67 | |
| Long chain fatty acid | 10-heptadecenoate (17:1n7) | 0.71 | 0.68 | 0.74 | |
| 10-nonadecenoate (19:1n9) | 0.57 | 0.51 | 0.65 | ||
| dihomo-linoleate (20:2n6) | 0.75 | 0.67 | 0.85 | ||
| dodecanedioate | 0.91 | 0.89 | 0.92 | ||
| eicosenoate (20:1n9 or 11) | 0.74 | 0.73 | 0.75 | ||
| linoleate (18:2n6) | 0.82 | 0.78 | 0.86 | ||
| myristate (14:0) | 0.60 | 0.54 | 0.66 | ||
| myristoleate (14:1n5) | 0.45 | 0.32 | 0.62 | ||
| oleate (18:1n9) | 0.67 | 0.60 | 0.76 | ||
| palmitate (16:0) | 0.80 | 0.80 | 0.81 | ||
| palmitoleate (16:1n7) | 0.52 | 0.45 | 0.58 | ||
| stearate (18:0) | 0.87 | 0.84 | 0.92 | ||
| Lysolipid | 1-arachidonoylglycerophosphocholine* | 0.74 | 0.77 | 0.70 | |
| 1-arachidoylglycerophosphocholine | 0.94 | 1.46 | 0.74 | ||
| 1-docosahexaenoylglycerophosphocholine* | 0.80 | 0.85 | 0.73 | ||
| 1-eicosatrienoylglycerophosphocholine* | 0.63 | 0.78 | 0.49 | ||
| 1-heptadecanoylglycerophosphocholine | 0.87 | 0.85 | 0.95 | ||
| 1-linoleoylglycerophosphoinositol* | 1.48 | 1.80 | 1.24 | ||
| 1-myristoylglycerophosphocholine | 0.86 | 0.94 | 0.73 | ||
| 1-oleoylglycerophosphate | 0.96 | 1.03 | 0.92 | ||
| 1-palmitoylglycerophosphate | 0.90 | 0.93 | 0.88 | ||
| 1-palmitoylglycerophosphocholine | 0.83 | 0.90 | 0.76 | ||
| 1-palmitoylglycerophosphoinositol* | 1.03 | 0.80 | 1.16 | ||
| 1-stearoylglycerophosphocholine | 0.82 | 0.88 | 0.74 | ||
| 2-linoleoylglycerophosphocholine* | 0.89 | 1.03 | 0.70 | ||
| 2-palmitoylglycerophosphocholine* | 0.75 | 0.92 | 0.57 | ||
| 2-stearoylglycerophosphocholine* | 0.76 | 0.78 | 0.70 | ||
| Medium chain fatty acid | laurate (12:0) | 1.03 | 0.90 | 1.25 | |
| pelargonate (9:0) | 0.98 | 0.98 | 0.99 | ||
| Monoacylglycerol | 1-stearoylglycerol (1-monostearin) | 1.00 | 1.16 | 0.88 | |
| Sterol/Steroid | 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca) | 1.12 | 1.13 | 1.09 | |
| campesterol | 0.68 | 1.20 | 0.39 | ||
| cholesterol | 0.99 | 1.07 | 0.95 | ||
| corticosterone | 1.87 | 1.94 | 1.72 | ||
| Energy | Krebs cycle | alpha-ketoglutarate | 0.55 | 0.66 | 0.46 |
| cis-aconitate | 1.21 | 1.15 | 1.28 | ||
| citrate | 1.31 | 1.21 | 1.43 | ||
| succinate | 1.04 | 1.31 | 0.83 | ||
| Oxidative phosphorylation | phosphate | 0.70 | 0.72 | 0.67 | |
| pyrophosphate (PPi) | 0.49 | 0.56 | 0.35 | ||
| Cofactors and vitamins | Ascorbate and aldarate metabolism | ascorbate (Vitamin C) | 0.56 | 0.80 | 0.37 |
| gulono-1,4-lactone | 1.10 | 0.99 | 1.16 | ||
| threonate | 1.00 | 0.90 | 1.11 | ||
| Nicotinate and nicotinamide metabolism | nicotinamide | 0.55 | 0.63 | 0.46 | |
| trigonelline (N’-methylnicotinate) | 1.30 | 1.31 | 1.30 | ||
| Pantothenate and CoA metabolism | pantothenate | 1.07 | 1.20 | 0.91 | |
| Xenobiotics | Benzoate metabolism | 4-ethylphenylsulfate | 0.51 | 1.03 | 0.03 |
| 4-vinylphenol sulfate | 2.42 | 3.31 | 1.73 | ||
| catechol sulfate | 1.57 | 2.21 | 1.11 | ||
| Chemical | methyl-alpha-glucopyranoside | 0.30 | 0.24 | 0.33 | |
| Food component/Plant | daidzein | 3.26 | 3.37 | 3.21 | |
| Sugar, sugar substitute, starch | erythritol | 1.16 | 1.24 | 1.11 |