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. Author manuscript; available in PMC: 2023 May 12.
Published in final edited form as: Nat Rev Chem. 2023 Mar 20;7(5):355–373. doi: 10.1038/s41570-023-00476-z

Table 1 |.

Diseases and their associated abnormal chiral biomarkers

Disease Biomarkers Location Concentrations in healthy subjects Concentrations in patients
Cancer Amino acids d-Pro Gastric juice 6–30 μM (ref.111)a 2–110 μM (ref.111)a
Saliva 0–11.3 μM (ref.207)b 22.5–112.6 μM (ref.207)b
d-Ala Gastric juice 5–24 μM (ref.111)a 20–280 μM (ref.111)a
Saliva 0–25.3 μM (ref.207)b 50.6–253.2 μM (ref.207)b
d-GLu Gastric juice 0–0.8 μM (ref.111)a 0.4–1.7μM (ref.111)a
Serum 0.003–0.008 μM (ref.112)c 0.002–0.004 μM (ref.112)c
d-Ser Gastric juice 0.3–5.7 μM (ref.111)a 2–34 μM (ref.111)a
d-Gln Serum 0.013–0.03 μM (ref.112)c 0.005–0.019 μM (ref.112)c
Organic acids d-2-HG Urine 2.8–17 mmolmol−1 (ref.181)d
2.5–12 mmolmol−1 (ref.104)c 		4.1–2,668 mmolmol−1 (ref.181)d
146–995 mmolmol−1 (ref.267)c
Serum 1–1.2 μM (ref.268)d
0.5–0.8 μM (ref.269)c 		0.7–4.4 μM (ref.268)d
2.3–28 μM (ref.269)c
Plasma 0.3–0.9 μM (ref.181)d
0–26 μM (ref.270)d
0.1–0.4 μM (ref.109)c 		0.3–73 μM (ref.181)d
l-2-HG Urine 2.4–14 mmolmol−1 (ref.104)c
1.3–19 mmolmol−1 (ref.271)d
0–52 mmolmol−1 (ref.181)d 		2–22 mmolmol−1 (ref.104)c
4.1–2,742 mmolmol−1 (ref.271)d
41–158 mmolmol−1 (ref.267)c
121–471 mmolmol−1 (ref.272)c
Serum 1–1.22 μM (ref.268)d
0.4–0.8 μM (ref.269)c
0–1.2 μM (ref.269)d 		1.2–5.8 μM (ref.268)d
0.4–2.1 μM (ref.269)c
Plasma 0.5–1.0 μM (ref.181)d 0.3–1.7 μM (ref.181)d
Brain diseases Amino acids d-Asp Grey matter 15–22.2 nmolg−1 (ref.84)b 8.9–20.7 nmolg−1 (ref.84)b
White matter 17.8–27 nmolg−1 (ref.84)b 3.9–17.1 nmolg−1 (ref.84)b
0.5–2.0 μM (ref.180)b
0.5–1.6 μM (ref.273)e 		1.2–5.4 μM (ref.180)b
d-Ala Grey matter 16–26 nmolg−1 (ref.84)b 7–12 nmolg−1 (ref.84)b
White matter 2–23 nmolg−1 (ref.84)b 6–21 nmolg−1 (ref.84)b
d-Ser Serum 1.7–2.9 μM (ref.56)c
0.9–2.2 μM (ref.72)a
1.0–2.9 μM (ref.134)d
1.5–2.8 μM (ref.274)c 		1.3–2.4 μM (ref.56)c
0.8–3.2 μM (ref.72)a
1.4–2.4 μM (ref.274)c
Plasma 1.4–2.5 μM (ref.275)a
1.7–2.9 μM (ref.276)a
0.6–1.3 μM (ref.277)c 		1.2–4.2 μM (ref.275)a
CSF 0.6–3.0 μM (ref.180)b
1.8–11.7 μM (ref.278)d
1.1–1.6 μM (ref.71)c
1.4–2.2 μM (ref.33)b 		4.9–13.1 μM (ref.180)b
1.3–1.9 μM (ref.71)c
0.9–1.8 μM (ref.33)b
Totalf CSF 12.5–23.3 μM (ref.180)b 18.8–34 μM (ref.180)b
Organic acids d-2-HG CSF 0.07–0.3 μM (ref.17)d 0.42–6 μM (ref.17)d
Plasma 0.3–0.9 μM (ref.181)d
0–26 μM (ref.270)d
0.1–0.4 μM (ref.109)c 		2.2–26 μM (ref.17)d
2.5–17 μM (ref.91)d
Urine 2.8–17 mmolmol−1 (ref.181)d
2.5–12 mmolmol−1 (ref.104)c 		228–750 mmolmol−1 (ref.17)d
18–1,185 mmolmol−1 (ref.91)d
l-2-HG Plasma 0.5–1.0 μM (ref.181)d 1.1–3.0 μM (ref.17)d
2.2–3.7 μM (ref.91)d
Urine 2.4–14 mmolmol−1 (ref.104)c
1.3–19 mmolmol−1 (ref.271)d
0–52 mmolmol−1 (ref.181)d 		630–1,420 mmolmol−1 (ref.279)d
1,000–5,520 mmolmol−1 (ref.280)c
25.2–430 mmol mol−1 (ref.91)d
671–3,392 mmol mol−1 (ref.281)d
Kidney diseases and diabetes Amino acids d-Asn Plasma 0–0.12 μM (ref.277)c
0.02–0.18 μM (ref.277)c 		0.14–0.36 μM (ref.186)c
d-Ser Plasma 1.4–2.5 μM (ref.275)a
1.7–2.9 μM (ref.276)a
0.6–1.3 μM (ref.277)c 		1.76–3.13 μM (ref.186)c
d-Ala Plasma 0–0.14 μM (ref.277)c
1.21–2.43 μM (ref.282)e 		1.18–4.73 μM (ref.186)c
Nail 0–14.6 pmolmg−1 (ref.101)c 3.6–49.5 pmolmg−1 (ref.101)c
d-Pro Plasma 0–0.7 μM (ref.186)c
0.15–0.56 μM (ref.277)c 		0.80–0.88 μM (ref.186)c
Nail 0.3–2.3 pmolmg−1 (ref.101)c 0–7.8 pmolmg−1 (ref.101)c
d-Tyr Plasma 0.7–1.1 μM (ref.100)b
0–0.12 μM (ref.277)c 		0.8–5.6 μM (ref.100)b
d-Phe Plasma 0.3–0.7 μM (ref.100)b
0.10–0.30 μM (ref.277)c 		0.1–3.5 μM (ref.100)b
d-Val Nail 0.1–0.4 pmolmg−1 (ref.101)c 0–14.8 pmolmg−1 (ref.101)c
d-Ile Nail 0.1–0.4 pmolmg−1 (ref.101)c 0–6.4 pmolmg−1 (ref.101)c
d-Leu Nail 1.3–3.8 pmolmg−1 (ref.101)c 0–35.6 pmolmg−1 (ref.101)c
Organic acids d-Lac Plasma 7.4–8.6 μM (ref.283)c
21.0–25.0 μM (ref.284)b 		9.5–11.9 μM (ref.283)c
15.9–63.3 μM (ref.18)b
Urine 0.9–1.3 mmolmol−1 (ref.283)c
6.2–30.2 mmolmol−1 (ref.18)b 		2.3–3.9 mmolmol−1 (ref.283)c
11.7–60.1 mmolmol−1 (ref.18)b
Saliva 0.02–0.11 μM (ref.285)c 0.00–0.96 μM (ref.285)c
d-HA Saliva 0.02–0.10 μM (ref.285)c 0.13–0.34 μM (ref.285)c
d-2-HG Urine 2.8–17 mmolmol−1 (ref.181)d
2.5–12 mmolmol−1 (ref.104)c 		0.2–16.5 mmolmol−1 (ref.104)c
l-2-HG Urine 2.4–14 mmolmol−1 (ref.104)c
1.3–19 mmolmol−1 (ref.271)d
0–52 mmolmol−1 (ref.181)d 		0.1–22.5 mmolmol−1 (ref.104)c

2-HG, 2-hydroxyglutarate; CSF, cerebrospinal fluid; d-HA, d-3-hydroxybutyric acid; d-Lac, d-lactate.

a

Concentrations determined by liquid chromatography–fluorescence.

b

Concentrations determined by enzymatic assay.

c

Concentrations determined by liquid chromatography–mass spectrometry.

d

Concentrations determined by gas chromatography–mass spectrometry.

e

Concentrations determined by capillary electrophoresis–fluorescence.

f

Total concentration of d-amino acids.