Table S6. Classification of altered pathways: TBI placebo vs. TBI probenecid + NAC
Biochemical Process Mode Pathways
Glutathione
detoxification/regeneration
-
Ascorbate recycling (cytosolic); Glutathione redox reactions II; Glutathione redox reactions I; Arsenate detoxification I (glutaredoxin); Methylglyoxal degradation I;
Formaldehyde oxidation; 4-hydroxy-2-nonenal detoxification.
+
Ascorbate recycling (cytosolic); 4-hydroxy-2-nonenal detoxification; Methylglyoxal degradation I; Formaldehyde oxidation; Glutathione redox reactions II; Glutathione redox reactions I.
Purine and pyrimidine nucleotides and nucleosides
metabolism
-
Pyrimidine deoxyribonucleatides de novo biosynthesis; Urate biosynthesis/inosine phosphate degradation; Pyrimidine deoxyribonucleatides biosynthesis from CTP;
Guanosine ribonucleotides de novo biosynthesis; Pyrimidine deoxyribonucleatides phosphorylation; Adenosine ribonucleotides de novo biosynthesis; Guanosine nucleotides degradation; Adenosine nucleotides degradation.
+
Pyrimidine deoxyribonucleatides biosynthesis from CTP; CMP phosphorylation;
Urea cycle; Urate biosynthesis/inosine phosphate degradation; Pyrimidine
deoxyribonucleatides phosphorylation; Pyrimidine deoxyribonucleatides de novo biosynthesis; Purine deoxyribonucleosides salvage; Guanosine ribonucleotides de novo biosynthesis; Pyrimidine ribonucleosides salvage I; Purine
deoxyribonucleosides degradation; UTP and CTP dephosphorylation I; Oxidized GTP and dGTP detoxification; 7-(3-amino-3-carboxypropyl)-wyosine biosynthesis;
Guanosine nucleotides degradation.
Catabolism/salvage/formati on of amino acids,
cathecolamines, co-factors, hormones, peptide and polyamines.
-
Noradrenaline and adrenaline degradation; dopamine degradation; lysine
degradation I (saccharopine pathway), serotonin degradation; lysine degradation II (pipecolate pathway); 2-amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA; histamine degradation; L-carnitine biosynthesis; tryptophan
degradation via tryptamine; L-dopa degradation; folate transformations I; nicotine degradation IV.
+ Melatonin degradation II; 4-hydroxyproline degradation; Putrescine degradation II;
Serine biosynthesis (phosphorylated route); Nicotine degradation IV; Melatonin degradation III; citrulline-nitric oxide cycle; 4-hydroxybenzoate biosynthesis; L- carnitine biosynthesis; Tryptophan degradation to a2-amino-3—caryboxymuconate semialdehyde; Nicotine degradation III; thyronamine and iodothyronamine
1
metabolism; asparagine degradation; Thiamine salvage; Thymine degradation; NAD salvage; malate-aspartate shuttle; diphthamide biosynthesis; tetrahydrobiopterin de novo biosynthesis; L-dopa degradation; lysine degradation I (saccharopine pathway);
valine degradation; L-cysteine degradation I; asparagine biosynthesis; histamine degradation; thyroid hormone metabolism II (via conjugation and/or degradation).
Fatty Acid or other lipid oxidation/degradation/biosy
nthesis
- Dolichol and dolichyl phosphate biosynthesis; Phospholipases; Epoxysqualene biosynthesis; Docosahexaenoate biosynthesis III (mammals); Palmitate biosynthesis;
+
fatty acid α-oxidation; Estradiol biosynthesis I; Zymosterol biosynthesis; trans, trans-farnesyl diphosphate biosynthesis; fatty acid α-oxidation III; Epoxysqualene biosynthesis; fatty acid β-oxidation (peroxisome); fatty acid β-oxidation; lipoate biosynthesis and incorporation; androgen biosynthesis; Dolichol and dolichyl phosphate biosynthesis; vitamin D3 biosynthesis.
Saccharides, glycolysis, Acetyl CoA and energy
processing
-
Pentose phosphate pathway (oxidative branch); NAD phosphorylation and dephosphorylation; GDP-L-fucose biosynthesis I (from GDP-D-mannose); TCA cycle; methylglyoxal III; D-glucoronate degradation; Leukotriene biosynthesis;
+
2-oxoisovalerate decarboxylation to isobutanoyl-CoA; ketolysis; TCA cycle; acetate conversion to acetyl-CoA; biotin-carboxyl carrier protein assembly; 2-oxoglutarate decarboxylation to succinyl-CoA;
Other
-
Sulfate activation for sulfonation; The visial cycle I (vertebrates); oxidative ethanol degradation III; phytol degradation; ethanol degradation II; ethanol degradation IV;
ubiquinol-10 biosynthesis.
+
Morphine biosynthesis; N-acetylglucosamine degradation I;
Geranylgeranyldiphosphate biosynthesis; tRNA splicing; ethanol degradation II;
ethanol degradation IV; Molybdenum cofactor biosynthesis; Terminal O-glycans residues modification; Mucin core 1 and core 2 O-glycosylation; oxidative ethanol degradation III; ubiquinol-10 biosynthesis; α-tocopherol degradation.
2