Metabolomics Point out the Effects of Carfilzomib on Aromatic Amino Acid Biosynthesis and Degradation
Abstract
:1. Introduction
2. Results
2.1. Post Hoc Analysis
2.2. Identification
3. Discussion
3.1. Patterns of Cfz-Induced Metabolic Regulation
3.2. Biomarkers of Cfz Nephrotoxicity
- Nine metabolites participate in the tryptophan (Trp) degradation pathway, i.e., tryptophan, 3-indole-propionic acid, 1H-indole-3-carboxaldehyde, 2-aminomuconic acid semialdehyde, 5-hydroxykynurenamine, indole, indoleacrylic acid, indolelactic acid, N′-formylkynurenine.
- Four metabolites are hydroxy fatty acids (HFAs), i.e., (S)-3,4-dihydroxybutyric acid, 3-hydroxydodecanoic acid, and 4-8-hydroxy-5,6-octadienoic acid were upregulated; whereas 3-hydroxyvalproic acid was downregulated.
- Three metabolites are FA derivatives, i.e., 3,5-tetradecadiencarnitine, hydroxypropionylcarnitine, and 3-hydroxyglutaric acid lactone.
- Two metabolites are medium- and long-chain fatty acids, i.e., 10Z-heptadecenoic acid and palmitic acid were found with increased levels; and three, i.e., heptenoic acid, 7,8-dihydropteroic acid, and 3,4-methylenesebacic acid, were found to have decreased.
3.3. Dysregulation of Fatty Acids Oxidation
3.4. Dysregulated Metabolic Pathways
3.5. Dysregulation of Biosynthesis and Metabolism of Phenylalanine
3.6. Dysregulation of Tryptophan Metabolism
3.6.1. Kynurenine Sub-Pathway of Trp Catabolism
3.6.2. Indole-Pyruvate Sub-Pathway of Trp Catabolism
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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R2(Y) PLSDA | Q2 PLSDA | R2(Y) PERMUT. | Q2 PEMUT. | AUC ROC’ PLSDA | Miss CLAS. Error (CFZ) (%)/PLS-DA | |
---|---|---|---|---|---|---|
Plasma (+) | 1 | 0.93 | 1 | 0.89 | 1 | 0 |
Kidney (+) | 0.99 | 0.88 | 0.98 | −0.23 | 1 | 0 |
Urine (+) | 0.99 | 0.94 | 0.93 | 0.063 | 1 | 0 |
Plasma (−) | 0.98 | 0.62 | 0.97 | 0.32 | 1 | 0 |
Kidney (−) | 0.99 | 0.77 | 0.93 | 0.01 | 1 | 0 |
Urine (−) | 0.99 | 0.82 | 0.93 | 0.13 | 1 | 0 |
Dataset | Metabolite | Regulation (Cfz) | AUC | p Value | VIP | Comment |
---|---|---|---|---|---|---|
kidney (−) | D-(+)-Galactose | ↓ | 0.9 | 0.0306 | 2 | |
kidney (−) | D-(+)-Galacturonic acid | ↓ | 0.9 | 0.0186 | 2 | |
kidney (−) | D-Glucuronic acid | ↓ | 0.9 | 0.0785 | 2 | |
kidney (−) | L-Phenylalanine | ↑ | 0.8 | 0.8056 | 2 | |
kidney (−) | Maleic acid | ↑ | 0.8 | 0.0388 | 2 | |
kidney (+) | [(S)-3-Hydroxy-N-methylcoclaurine + NH] | ↑ | 1 | 0.0044 | 2 | * |
kidney (+) | [166.4847_6.96] | ↑ | 0.9 | 0.0118 | 2 | * |
kidney (+) | [166.8851_6.95] | ↑ | 1 | 0.0037 | 2 | * |
kidney (+) | [4-Ethylbenzoic acid + NH] | ↑ | 0.8 | 0.027 | 2 | * |
kidney (+) | [86.3838_6.94] | ↑ | 0.9 | 0.028 | 2 | * |
kidney (+) | [L-Tyrosine-O] | ↑ | 0.8 | 0.027 | 2 | * |
kidney (+) | 1-Phenylethylamine | ↑ | 0.9 | 0.0065 | 2 | |
kidney (+) | 2-Methylglutaric acid | ↓ | 0.9 | 0.0191 | 2 | |
kidney (+) | 3-Methylglutaric acid | ↓ | 0.9 | 0.0191 | 2 | |
kidney (+) | 4-Quinolinecarboxylic acid | ↓ | 0.9 | 0.0144 | 2 | |
kidney (+) | Adipic acid | ↓ | 0.9 | 0.0191 | 2 | |
kidney (+) | Cortexolone | ↑ | 0.9 | 0.0143 | 2 | |
kidney (+) | DL-Normetanephrine | ↑ | 0.8 | 0.027 | 2 | |
kidney (+) | Hippuric acid | ↓ | 1 | 0.0062 | 2 | |
kidney (+) | L-Asparagine | ↑ | 0.9 | 0.0142 | 2 | |
kidney (+) | L-Phenylalanine | ↑ | 0.8 | 0.027 | 2 | |
kidney (+) | NG,NG-Dimethylarginine | ↑ | 0.9 | 0.003 | 2 | |
kidney (+) | NG,NG′-Dimethyl-L-arginine | ↑ | 0.9 | 0.003 | 2 | |
kidney (+) | Perillyl alcohol | ↓ | 0.9 | 0.0196 | 1 | |
kidney (+) | Pyridoxamine | ↑ | 0.9 | 0.0 | 1.8 | |
kidney (+) | Quinaldic acid | ↓ | 0.9 | 0.0 | 1.6 | |
plamsa (+) | L-Homoserine | ↓ | 0.8 | 0.2906 | 2 | |
plamsa (+) | L-Methionine | ↓ | 0.8 | 0.1365 | 2 | |
plamsa (+) | L-Threonine | ↓ | 0.8 | 0.2604 | 2 | |
plamsa (+) | N1-Methyl-2-pyridone-5-carboxamide | ↑ | 0.9 | 0.03 | 2 | |
plasma (−) | N-Acetyl-L-leucine | ↓ | 0.9 | 0.0027 | 2 | |
urine (−) | D-(+)-Galactose | ↑ | 0.9 | 0.0156 | 1 | |
urine (−) | Methylmalonic acid | ↓ | 1 | 0.003 | 2 | |
urine (−) | Nonanoate | ↓ | 1 | 0.0019 | 2 | |
urine (+) | (R)-Salsolinol | ↓ | 1.0 | 0.0 | 2.0 | * |
urine (+) | [(R)-Salsolinol + C3H5NOS] | ↓ | 1.0 | 0.0 | 2.0 | * |
urine (+) | [4-Ethylbenzoic acid + NH] | ↓ | 0.9 | 0.0274 | 2 | * |
urine (+) | [L-Tyrosine-O] | ↓ | 0.9 | 0.0274 | 2 | * |
urine (+) | [Pipecolic acid + C4H3N3] | ↓ | 0.9 | 0.0077 | 2 | * |
urine (+) | [p-Synephrine + NH] | ↑ | 0.9 | 0.0032 | 2 | * |
urine (+) | 1-Methyladenosine | ↑ | 0.9 | 0.0221 | 2 | |
urine (+) | 3-Amino-4-hydroxybenzoic acid | ↑ | 0.8 | 0.0254 | 2 | |
urine (+) | 4-COUMARATE | ↓ | 0.8 | 0.0285 | 2 | |
urine (+) | 4-Ethylbenzoic acid | ↓ | 0.9 | 0.0108 | 2 | |
urine (+) | 5-Hydroxy-L-tryptophan | ↓ | 0.9 | 0.0215 | 2 | |
urine (+) | Argininic acid | ↑ | 1 | 0.0245 | 2 | |
urine (+) | DL-Normetanephrine | ↓ | 0.9 | 0.0274 | 2 | |
urine (+) | L-Citrulline | ↑ | 1 | 0.026 | 2 | |
urine (+) | L-Phenylalanine | ↓ | 0.9 | 0.0274 | 2 | |
urine (+) | L-Tyrosine | ↓ | 0.9 | 0.0074 | 2 | |
urine (+) | Lumazine | ↓ | 0.9 | 0.0125 | 2 | |
urine (+) | L-Valine | ↓ | 0.9 | 0.0174 | 2 | |
urine (+) | N(6)-Methyllysine | ↑ | 0.9 | 0.005 | 2 | |
urine (+) | N-Acetyl-5-hydroxytryptamine | ↓ | 1 | 0.0012 | 2 | |
urine (+) | N-Methyltryptamine | ↓ | 0.9 | 0.0192 | 2 | |
urine (+) | Salsolinol | ↓ | 1.0 | 0.0 | 2.0 | |
urine (+) | Tyramine | ↓ | 0.9 | 0.0 | 1.7 |
Biosample | m/z | RT | Formula | Error (mDa) | Score (MS1) | Regulation (Cfz) | Compound | Score (MS2) | Adduct Type | Library | Reaction |
---|---|---|---|---|---|---|---|---|---|---|---|
Kidney | 205.0991 | 3.61 | C11H11NO2 | −0.0025 | 1 | ↑ | 3-Indolepropionic acid | 0.93 | [M + H]+ | One-Reaction/MCID | [+NH] |
Kidney | 175.1204 | 1.29 | C7H16NO2 | −0.00065 | 1 | ↑ | Acetylcholine | 0.77 | [M + H]+ | One-Reaction/MCID | [+CO] |
Urine | 156.9912 | 1.72 | C4H8O4 | −1.4 | 4.1 | ↑ | (S)-3,4-Dihydroxybutyric acid | 7.2 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 308.1059 | 4.99 | C12H21NO4S2 | −7 | 3.7 | ↑ | (S)-Succinyldihydrolipoamide | 6.1 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 267.236 | 13.65 | C17H32O2 | −3 | 5.1 | ↑ | 10Z-Heptadecenoic acid | 7 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 144.0475 | 5.51 | C9H7NO | −2.3 | 4 | ↓ | 1H-Indole-3-carboxaldehyde | 7.4 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 601.3402 | 3.31 | C27H53O12P | −5.1 | 3.8 | ↑ | 1-Stearoylglycerophosphoinositol | 6.3 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 142.0492 | 1.31 | C6H7NO3 | 0.7 | 3.6 | ↑ | 2-Aminomuconic acid semialdehyde | 6 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 129.0202 | 1.2 | C5H6O4 | −1.5 | 3.7 | ↓ | 2-Hydroxyglutaric acid lactone | 6.3 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 170.0618 | 3.64 | C8H11NO | −3.97609 | 1 | ↑ | 2-Hydroxyphenethylamine | 0.77 | [M + H]+ | One-Reaction/MCID | [+CO] |
Urine | 368.2815 | 10.81 | C21H37NO4 | −2.2 | 4 | ↑ | 3,5-Tetradecadiencarnitine | 7.05 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 227.1292 | 4.64 | C12H18O4 | −1.5 | 3.8 | ↓ | 3,4-Methylenesebacic acid | 6.4 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 245.183 | 1.26 | C12H24O3 | −0.00881 | 1 | ↑ | 3-Hydroxydodecanoic acid | 0.65 | [M + H]+ | One-Reaction/MCID | [+CO] |
Urine | 219.1172 | 3.94 | C10H18O5 | 5 | 3.7 | ↓ | 3-Hydroxysebacic acid | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 161.1088 | 4.89 | C8H16O3 | −1.4 | 3.7 | ↓ | 3-Hydroxyvalproic acid | 6.69 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 130.0665 | 5.58 | C9H7N | −1.3 | 4.3 | ↓ | 3-Methylene-indolenine | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 259.0945 | 2.81 | C10H14N2O6 | −4 | 4.1 | ↓ | 3-Methyluridine | 6.6 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 129.0926 | 4.46 | C7H12O2 | −1.5 | 4 | ↓ | 4-Heptenoic acid | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 409.1928 | 3.61 | C11H21N3O5 | 0.000894 | 1 | ↑ | 5-Acetamidovalerate | 0.7 | [M + H]+ | One-Reaction/MCID | [+C5H3N5] |
Urine | 296.067 | 2.09 | C8H14N3O7P | −3 | 4 | ↓ | 5-Aminoimidazole ribonucleotide | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 296.0681 | 1.24 | C8H14N3O7P | −3.7 | 3.4 | ↑ | 5-Aminoimidazole ribonucleotide | 5.4 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 181.0987 | 2.51 | C9H12N2O2 | −1.5 | 4 | ↓ | 5-Hydroxykynurenamine | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 181.0879 | 2.26 | C9H12N2O2 | 10 | 4.2 | ↑ | 5-Hydroxykynurenamine | 7.2 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 181.0874 | 2.27 | C9H12N2O2 | 9.75 | 3.2 | ↑ | 5-Hydroxykynurenamine | 5.2 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 321.045 | 5.61 | C10H15N2O8P | 4.3 | 4 | ↑ | 5-Thymidylic acid | 6.7 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 212.0781 | 1.52 | C7H9N5O3 | −1.4 | 3.7 | ↓ | 6-Carboxy-5,6,7,8-tetrahydropterin | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 315.1123 | 5.19 | C14H14N6O3 | 7.4 | 3.7 | ↓ | 7,8-Dihydropteroic acid | 6.3 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 157.0848 | 3.62 | C8H12O3 | 1.1 | 4.3 | ↑ | 8-Hydroxy-5,6-octadienoic acid | 67 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 220.065 | 5.12 | C11H9NO4 | −4 | 3.5 | ↓ | 8-Methoxykynurenate | 5.5 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 117.0587 | 3.62 | C5H8O3 | −4 | 3.7 | ↑ | Alpha-ketoisovaleric acid | 7 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 221.0701 | 5.49 | C7H12N2O6 | 6 | 3.5 | ↓ | Aspartyl-Serine | 6.02 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 130.062 | 1.55 | C4H9N3O2 | 0.4 | 4.7 | ↑ | Beta-Guanidinopropionic acid | 7.7 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 149.0612 | 3.06 | C9H8O2 | −1.6 | 3.7 | ↑ | Cinnamic acid | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 132.083 | 3.62 | C4H9N3O2 | −5.3 | 3.9 | ↑ | Creatine | 8.2 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 112.0516 | 2.4 | C4H5N3O | −0.8 | 3.5 | ↓ | Cytosine | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 227.0721 | 9.32 | C9H12N2O5 | −4.6 | 0.1 | ↑ | Deoxyuridine | 7.9 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 199.0076 | 4.81 | C4H9O7P | −6.3 | 3.9 | ↑ | D-Erythrose 4-phosphate | 6.7 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 240.1038 | 2.63 | C9H13N5O3 | 5 | 4.1 | ↑ | Dihydrobiopterin | 7.6 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 433.1156 | 4.13 | C21H20O10 | −2.9 | 3.9 | ↑ | Dihydrodaidzein 7-O-glucuronide | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 160.1348 | 1.61 | C8H17NO2 | −1.6 | 4 | ↑ | DL-2-Aminooctanoic acid | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 160.1339 | 1.36 | C8H17NO2 | 0.79 | 4 | ↑ | DL-2-Aminooctanoic acid | 7.23 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 229.0189 | 4.78 | C5H11O8P | −6.2 | 4.6 | ↑ | D-Ribose 5-phosphate | 8.3 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 419.1381 | 4.96 | C21H22O9 | −4.4 | 3.6 | ↑ | Equol 7-O-glucuronide | 6.41 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 276.1033 | 1.77 | C12H13N5O3 | 5.5 | 3.5 | ↓ | Ethenodeoxyadenosine | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 457.1166 | 4.26 | C17H21N4O9P | −3.9 | 4.1 | ↑ | Flavin Mononucleotide | 7.1 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 261.148 | 3.72 | C11H20N2O5 | −3.4 | 4 | ↑ | gamma-Glutamylisoleucine | 6.8 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 223.1097 | 3.24 | C11H14N2O3 | −2 | 3.9 | ↓ | Glycyl-Phenylalanine | 6.26 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 146.062 | 3.62 | C3H7N3O2 | −0.00653 | 1 | ↑ | Guanidoacetic acid | 0.23 | [M + H]+ | One-Reaction/MCID | [+CO] |
Kidney | 118.0666 | 3.62 | C3H7N3O2 | −5 | 3.8 | ↑ | Guanidoacetic acid | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 140.072 | 4.36 | C6H9N3O | −1.3 | 3.5 | ↓ | Histidinal | 5.8 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 213.0928 | 7.97 | C8H12N4O3 | 5 | 4.1 | ↓ | Histidinyl-Glycine | 6.6 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 183.0672 | 1.81 | C9H10O4 | −1.8 | 3.9 | ↓ | Homovanillic acid | 7.3 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 351.1743 | 4.96 | C10H19NO5 | 3.002896 | 1 | ↓ | Hydroxypropionylcarnitine | 0.97 | [M + H]+ | One-Reaction/MCID | [+(C5H5N5-H2O)] |
Kidney | 137.4083 | 2.41 | C5H4N4O | −1 | 4.2 | ↑ | Hypoxanthine | 8.4 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 157.0668 | 6.78 | C6H8N2O3 | −6 | 3.4 | ↓ | Imidazolelactic acid | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 116.0519 | 3.54 | C8H7N | −2.9 | 4.1 | ↑ | Indole | 8.07 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 331.1674 | 3.06 | C11H9NO2 | −0.00272 | 0.93 | ↑ | Indoleacrylic acid | 0.7 | [M + H]+ | One-Reaction/MCID | [+C7H13NO2] |
Urine | 206.0818 | 5.16 | C11H11NO3 | −0.5 | 4 | ↓ | Indolelactic acid | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 222.072 | 4.44 | C11H11NO3 | 0.003536 | 1 | ↓ | Indolelactic acid | 0.8 | [M + H]+ | One-Reaction/MCID | [+O] |
Urine | 245.0966 | 6.21 | C13H12N2O3 | −4.8 | 3.8 | ↓ | Indolylacryloylglycine | 5.8 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 310.0945 | 3.19 | C14H15NO7 | −2.5 | 4.2 | ↑ | Inodxyl glucuronide | 7 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 229.0608 | 2.76 | C11H20N2O3 | −0.9 | 3.6 | ↓ | Isoleucylproline | 6.8 | [M+Na]+ | HMDB (MSFINDER) | - |
Kidney | 173.1061 | 1.69 | C6H14N4O2 | −1.6 | 5.2 | ↑ | L-Arginine | 8.8 | [M − H]− | HMDB (MSFINDER) | - |
Kidney | 869.4803 | 5.67 | C40H72N2O18 | −0.5 | 3.5 | ↑ | Lc3Cer | 6 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 162.114 | 1.59 | C7H15NO3 | −1.4 | 4.1 | ↓ | L-Carnitine | 7.4 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 198.0775 | 4.36 | C9H11NO4 | −1.4 | 4.1 | ↓ | L-Dopa | 4.34 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 260.9009 | 1.18 | C11H21N3O4 | 8 | 3.8 | ↓ | Leucyl-Glutamine | 6.3 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 229.1557 | 1.96 | C11H20N2O3 | −0.63 | 4 | ↑ | Leucylproline | 7.2 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 322.1084 | 7.24 | C11H19N3O6S | −0.46 | 4 | ↓ | L-L-Homoglutathione | 6.34 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 203.0821 | 3.54 | C11H12N2O2 | −0.7 | 4.3 | ↑ | L-Tryptophan | 8.2 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 247.1092 | 4.95 | C10H18N2O3S | 1.3 | 3.7 | ↓ | Methionyl-Proline | 6.1 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 264.1019 | 3.15 | C11H15N5O4 | 0.007764 | 1 | ↓ | N6-Methyladenosine | 0.73 | [M + H]+ | One-Reaction/MCID | [-H2O] |
Kidney | 365.154 | 4.52 | C14H24N2O9 | 2.5 | 4.4 | ↓ | N-Acetylmuramoyl-Ala | 7.4 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 265.0966 | 3.15 | C5H9NO4 | 0.007765 | 1 | ↓ | N-Acetylserine | 0.67 | [M + H]+ | One-Reaction/MCID | [+(C5H5N5-H2O)] |
Urine | 175.1494 | 7.06 | C8H18N2O2 | −5 | 3.9 | ↓ | Ne,Ne dimethyllysine | 6.41 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 279.0938 | 4.01 | C11H12N2O4 | 0.003199 | 0.9 | ↓ | N′-Formylkynurenine | 0.6 | [M + H]+ | One-Reaction/MCID | [+C2H2O] |
Kidney | 131.0508 | 3.06 | C4H6N2O2 | −0.00623 | 1 | ↑ | N-Methylhydantoin | 0.6 | [M + H]+ | One-Reaction/MCID | [+O] |
Kidney | 613.1562 | 3.08 | C20H32N6O12S2 | 3 | 3.8 | ↑ | Oxidized glutathione | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 255.5898 | 13.86 | C16H32O2 | 0.15 | 4.3 | ↑ | Palmitic acid | 8.5 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 181.0662 | 6.79 | C7H8N4O2 | 5 | 3.8 | ↓ | Paraxanthine | 6.72 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 121.0658 | 7.97 | C8H8O | −0.8 | 4 | ↓ | Phenylacetaldehyde | 6.7 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 165.0564 | 1.85 | C9H8O3 | −1.4 | 3.7 | ↓ | Phenylpyruvic acid | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 165.0561 | 1.88 | C9H8O3 | −1.9 | 3.7 | ↑ | Phenylpyruvic acid | 6.4 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 304.1777 | 1.74 | C14H25NO6 | −2.2 | 3.9 | ↓ | Pimelylcarnitine | 6.74 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 230.1195 | 7.66 | C9H15N3O4 | −1.5 | 3.7 | ↓ | Prolyl-Asparagine | 5.85 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 131.1043 | 5.15 | C7H14O2 | 2.8 | 3.4 | ↓ | Propyl butyrate | 5.8 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 169.0985 | 2.99 | C8H12N2O2 | −1.2 | 3.8 | ↓ | Pyridoxamine | 6.9 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 201.1159 | 3.53 | C10H18O4 | −2.7 | 5.1 | ↓ | R-2-Hydroxy-3-methylbutanoic acid 3-Methylbutanoyl | 8.5 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 455.0823 | 3.44 | C13H19N4O12P | −0.8 | 3.8 | ↓ | SAICAR | 6.7 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 380.258 | 13.19 | C18H38NO5P | −3 | 4 | ↑ | Sphingosine 1-phosphate | 6.8 | [M + H]+ | HMDB (MSFINDER) | - |
Plasma | 190.0878 | 6.55 | C8H15NO2S | 1.4 | 4 | ↓ | S-Prenyl-L-cysteine | 6.2 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 99.0089 | 1.56 | C4H4O3 | −0.14 | 3.9 | ↓ | Succinic anhydride | 6.29 | [M − H]− | HMDB (MSFINDER) | - |
Urine | 391.176 | 7.67 | C22H22N4O3 | 0.4 | 3.9 | ↓ | Tryptophyl-Tryptophan | 6 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 113.0353 | 2.61 | C4H4N2O2 | −0.8 | 3.6 | ↓ | Uracil | 6.3 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 113.0361 | 1.93 | C4H4N2O2 | −1 | 4.2 | ↑ | Uracil | 7.12 | [M + H]+ | HMDB (MSFINDER) | - |
Kidney | 147.1143 | 1.3 | C5H10N2O4 | −1.5 | 3.8 | ↑ | Ureidoisobutyric acid | 7 | [M + H]+ | HMDB (MSFINDER) | - |
Urine | 139.0407 | 7.18 | C6H6N2O2 | −2 | 3.4 | ↓ | Urocanic acid | 6.5 | [M + H]+ | HMDB (MSFINDER) | - |
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Barla, I.; Efentakis, P.; Lamprou, S.; Gavriatopoulou, M.; Dimopoulos, M.-A.; Terpos, E.; Andreadou, I.; Thomaidis, N.; Gikas, E. Metabolomics Point out the Effects of Carfilzomib on Aromatic Amino Acid Biosynthesis and Degradation. Int. J. Mol. Sci. 2023, 24, 13966. https://doi.org/10.3390/ijms241813966
Barla I, Efentakis P, Lamprou S, Gavriatopoulou M, Dimopoulos M-A, Terpos E, Andreadou I, Thomaidis N, Gikas E. Metabolomics Point out the Effects of Carfilzomib on Aromatic Amino Acid Biosynthesis and Degradation. International Journal of Molecular Sciences. 2023; 24(18):13966. https://doi.org/10.3390/ijms241813966
Chicago/Turabian StyleBarla, Ioanna, Panagiotis Efentakis, Sofia Lamprou, Maria Gavriatopoulou, Meletios-Athanasios Dimopoulos, Evangelos Terpos, Ioanna Andreadou, Nikolaos Thomaidis, and Evangelos Gikas. 2023. "Metabolomics Point out the Effects of Carfilzomib on Aromatic Amino Acid Biosynthesis and Degradation" International Journal of Molecular Sciences 24, no. 18: 13966. https://doi.org/10.3390/ijms241813966