Table 1 Functional annotation of overlapped metabolite biomarkers between L-LH and H-HH sets.

1

Nicotinamide

Component of the coenzyme NAD, cofactor, antioxidant, neuroprotective agent, anti-inflammatory agent.

11.53

2.08

11.21

1.55

2

(-)-Naringenin

Inhibitor to cytochrome P450 isoform CYP1A2.

8.74

1.68

6.22

1.77

3

O-Acetyl-L-serine

Takes part in cysteine and glutathione metabolism.

5.16

2.2

5.47

1.78

4

Maleamic acid

Conjugate acid of a maleamate.

5.94

2.08

5.06

1.74

5

2-Methylbutyroylcarnitine^*

Intermediate of isoleucine metabolism.

9.55

2.36

4.55

2.25

6

Stearoylcarnitine^*

Metabolite biomarker suggests carnitine palmitoyltransferase (CPT) II deficiency.

4.15

1.97

3.71

2.46

7

1,3-Dimethyluric acid

Metabolite from the metabolism of methylxanthines (caffeine, theophylline, and theobromine) mainly catalyzed by CYP1A2.

3.54

2.21

3.59

2.26

8

Iminodiacetic acid

Chelator of Ca²⁺, Mg²⁺ and polymer to create an ion-exchange resin.

3.6

2.34

3.45

2.38

9

Imidazoleacetic acid

Metabolite product of histamine metabolism.

1.52

1.7

3.45

2.38

10

1,7-Dimethyluric acid

A metabolite from the metabolism of methylxanthines (caffeine, theophylline, and theobromine) mainly catalyzed by CYP1A2.

2.19

1.78

3.33

1.6

11

CDP-choline

Essential molecule for membranes biosynthesis and repair, molecule for neuroprotection.

2.72

2.26

3.11

2.12

12

Amrinone

Acardiotonic, vasodilator.

2.08

2.04

2.8

2.06

13

DL-Indole-3-lactic acid^*

Metabolite of tryptophan.

1.93

2.14

2.67

2.36

14

Suberic acid^*

Metabolite biomarker suggests deficiencies of medium-chain acyl-CoA dehydrogenase, carnitine-acylcarnitine translocase, or malonyl-CoA decarboxylase.

1.85

1.76

2.34

2.14

15

alpha-Guanidinoglutaric acid^*

Derivative of glutaric acid, which can induce seizures.

1.95

2.28

2.33

2.36

16

Creatine

Facilitator of ATP biosynthesis.

1.75

2.08

2.19

2.37

17

D-Biotin

An important component of enzymes involved in metabolizing fats and carbohydrates. Maintains cellular metabolism.

2.24

2.05

2.19

1.75

18

MDMA

Nervous stimulant. Facilitates ATP production.

1.96

2.16

2.11

2.24

19

Phenelzine

Non-selective and irreversible monoamine oxidase inhibitor, neuroregulator.

1.73

2.14

2.08

2.35

20

7-Methylxanthine

Metabolite from the metabolism of methylxanthines (caffeine, theophylline, and theobromine) mainly catalyzed by CYP1A2.

1.54

1.69

2.05

1.95

21

N-Acetyl-L-tyrosine^#

Metabolite biomarker suggests aromatic L-amino acid decarboxylase deficiency.

1.92

1.72

2.04

1.59

22

Acamprosate

Metabolite could stabilize the chemical balance with side effect of irregular heartbeats.

2.11

1.85

2.03

1.6

23

Erythrono-1,4-lactone

Lactone of tetronic acid.

2.07

2.42

1.79

2.29

24

5-Methylcytidine

Post-transcriptional modifications found in tRNA, snRNA, and rRNA.

1.86

2.21

1.72

1.95

25

5-Hydroxyindoleacetate^#

Metabolite involved in tryptophan metabolism. Breakdown product of serotonin.

1.98

1.75

1.72

1.84

26

Niflumic Acid

Inhibitor of chloride channels and T-type calcium channels. Inhibitor of phospholipase A2 and cyclooxygenase-2.

2.06

1.85

1.7

1.65

27

L-Kynurenine^*

Intermediate metabolite of tryptophan. Metabolite biomarker suggests kynurenine-3-monooxygenase deficiency.

1.81

2.18

1.64

1.73

28

L-Palmitoylcarnitine^*

Metabolite biomarker suggests carnitine palmitoyltransferase (CPT) II deficiency.

1.78

1.54

1.62

1.8