TABLE 1.
Potential biomarkers in copper-laden HLD hepatocytes detected by HILIC-Q-TOF/MS and their variation tendency (NEG and POS).
| No | Features (tR- m/z) | Cal. m/z | Delta m/z (ppm) | VIP | VIP a | Metabolite identification | Formula | Ion form | Fragment ions | Trend | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| C a /M b | M/G c | M/C | G/M | ||||||||
| 1 | 1.84_128.0349 | 128.0353 | 3.1 | 7.92 | 5.16 | Pyroglutamic acid | C5H7NO3 | M-H | 126.7031 | ↑ | ↓ |
| 2 | 1.85_133.0132 | 133.0142 | 7.5 | 5.21 | 2.55 | Malic acid | C4H6O5 | M-H | 115.0065 | ↓ | ↑ |
| 3 | 1.09_133.0135 | 133.0142 | 5.3 | 2.81 | 3.29 | Pyruvic acid | C3H4O3 | M + FA-H | 87.0082 | ↓ | ↑ |
| 4 | 5.24_168.0428 | 168.0431 | 1.8 | 1.55 | 2.13 | Phosphodimethylethanolamine | C4H12NO4P | M-H | 96.9607, 78.9591 | ↓ | ↑ |
| 5 | 1.55_174.0399 | 174.0408 | 5.2 | 4.70 | 3.33 | N-Acetyl-L-aspartic acid | C6H9NO5 | M-H | 130.0463, 88.0421 | ↑ | ↓ |
| 6 | 1.04_183.0665 | 183.0663 | 1.1 | 1.19 | 1.14 | Vanylglycol | C9H12O4 | M-H | 153.0552, 121.0281 | ↑ | ↑ |
| 7 | 1.07_192.0487 | 192.0508 | 0 | 2.00 | 1.50 | L-Glutamic acid | C5H9NO4 | M + FA-H | 127.9222, 123.9017, 74.0032 | ↑ | ↓ |
| 8 | 4.55_214.0485 | 214.0485 | 0 | 1.92 | 1.90 | Glycerylphosphorylethanolamine | C5H14NO6P | M-H | 168.9919, 96.9587, 78.9578 | ↑ | ↓ |
| 9 | 1.68_218.1020 | 218.1034 | 6.4 | 2.29 | 1.83 | Pantothenic acid | C9H17NO5 | M-H | 146.0817, 128.0600, 88.0399 | ↑ | ↓ |
| 10 | 5.28_242.0803 | 242.0782 | 8.7 | 3.62 | 3.56 | Cytidine | C9H13N3O5 | M-H | 168.0435, 112.9812 | ↓ | ↑ |
| 11 | 5.11_259.0226 | 259.0224 | 0.8 | 6.76 | 2.13 | D-Mannose 1-phosphate | C6H13O9P | M-H | 229.0061, 96.9607, 78.9578 | ↓ | ↑ |
| 12 | 5.35_273.0380 | 273.0380 | 0 | 1.82 | 1.56 | Mevalonic acid-5P | C6H13O7P | M + FA-H | 96.9587, 78.9578 | ↑ | ↓ |
| 13 | 4.91_346.0555 | 346.0558 | 0.9 | 1.73 | 1.22 | AMP | C10H14N5O7P | M-H | 134.0459, 96.9667, 78.9578 | ↑ | ↓ |
| 14 | 7.19_402.0094 | 402.0109 | 3.7 | 1.56 | 1.97 | CDP | C9H15N3O11P2 | M-H | 173.9330, 158.9236, 96.9667 | ↑ | ↓ |
| 15 | 8.13_426.0220 | 426.0220 | 0 | 7.58 | 3.35 | ADP | C10H15N5O10P2 | M-H | 426.0193, 158.9236 | ↓ | ↑ |
| 16 | 9.55_505.9878 | 505.9885 | 1.4 | 2.54 | 1.23 | ATP | C10H16N5O13P3 | M-H | 408.0143, 238.8838, 176.9303 | ↑ | ↓ |
| 17 | 5.70_662.1057 | 662.1018 | 5.9 | 5.94 | 2.90 | NAD | C21H27N7O14P2 | M-H | 425.9982, 78.9596 | ↓ | ↑ |
| 18 | 7.91_742.0680 | 742.0680 | 0 | 1.13 | 1.02 | NADP | C21H28N7O17P3 | M-H | 96.9687, 78.9578 | ↓ | ↑ |
| 19 | 1.01_138.0551 | 138.0561 | 7.2 | 1.23 | 1.28 | N-Acetyl-L-glutamate 5-semialdehyde | C7H11NO4 | M + H-2H2O | 138.0564, 130.0691 | ↑ | ↓ |
| 20 | 5.23_184.0754 | 184.0739 | 8.1 | 2.39 | 4.55 | Phosphorylcholine | C5H15NO4P | M + H | 124.9771, 98.9858, 84.0804 | ↓ | ↑ |
| 21 | 4.60_241.0339 | 241.0346 | 2.9 | 2.13 | 2.69 | L-Cystine | C6H12N2O4S2 | M + H | 177.0340, 149.0213, 122.0281 | ↑ | ↓ |
| 22 | 2.56_291.0716 | 291.070 | 5.5 | 2.51 | 1.82 | Inosine | C10H12N4O5 | M + Na | 133.0792 | ↑ | ↓ |
a
C means shNC, group.
b
M means shATP7B + Cu group.
c
G means GDD, group.
Change of potential biomarkers in copper-laden HLD, hepatocytes among groups were statistically analyzed by multivariate statistical analysis and ANOVA. Significant changed biomarkers were flagged with (↓) content decreased and (↑) content increased. p-values were calculated by Student's t-test (threshold < 0.05).