Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach
Abstract
:1. Introduction
2. Results
2.1. Participants
2.2. Metabolomic Analysis
2.2.1. Acetylcarnitine
2.2.2. Fumarate
2.2.3. Citrate
2.2.4. Isocitrate
2.2.5. Myo-Inositol
2.2.6. Glutamate
2.2.7. Pyruvate
2.2.8. Malate
2.2.9. Glycerol
2.2.10. Lactate
2.2.11. 2-Oxoglutarate
2.2.12. Acetoacetate
2.2.13. Succinate
2.2.14. 3-hydroxybutyrate
2.2.15. Glutarate
3. Discussion
3.1. First Carbon Oxidation Pathway of the TCA Cycle-Related Metabolites
3.2. Second Carbon Oxidation Pathway of the TCA-Cycle Related Metabolites
3.3. Glycolysis and Anaerobic Metabolism-Related Metabolites
3.4. Lipidic Metabolism-Related Metabolites
3.5. Amionoacidic Metabolism-Related Metabolites
3.6. Limitations
4. Materials and Methods
4.1. Study Design and Participants
4.2. Variables
4.3. Sample Preparation and Metabolomic Analysis
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Metabolite (µg/L) | Acetate Dialysate | Citrate Dialysate | ||
---|---|---|---|---|
Pre-Dialysis | Post-Dialysis | Pre-Dialysis | Post-Dialysis | |
Acetylcarnitine | 2292.83 (1698.3–3835.64) | 565.12 (75–814.56) | 2108.21 (1138.39–3206.01) | 164.52 (75–643.1) |
Fumarate | 1275.33 (940.83–1597.34) | 1215.87 (1050.27–1617.92) | 968.72 (682.95–1169.75) | 924.19 (790.46–1109.45) |
Citrate | 23,930.01 ± 6243.63 | 13,151.82 ± 3245.25 | 18,312.77 ± 5534.11 | 35,351.74 ± 6126.8 |
Isocitrate | 13,181.79 (11,407.72–15,441.07) | 6717.97 (6051.02–7927.15) | 15,438.28 (14,109.91–16,918.49) | 10,463.95 (9330.3–12,195.79) |
Myo-inositol | 186,825.86 (115,033.27–325,459.59) | 34,635.77 (4328.17–69,297.23) | 156,509.77 (123,131.02–315,150.31) | 31,586.57 (3125–55,889.43) |
Glutamate | 164.33 (112.36–260.19) | 242.62 (166.44–318.71) | 160.35 (102.76–204.39) | 239.09 (150.69–342.67) |
Pyruvate | 5075.38 (3526.28–6168.7) | 3509.35 (2905.18–3952.23) | 4253.1 (3135.06–5031.68) | 3322.45 (2664.53–5529.55) |
Malate | 1418.21 (1015.39–1760.36) | 1418.82 (1138.72–1869.07) | 1080.15 (860.11–1416.11) | 1238.32 (879.48–1496.05) |
Glycerol | 48.5 (48.5–48.5) | 48.5 (48.5–48.5) | 48.5 (48.5–129.6) | 48.5 (48.5–48.5) |
Lactate | 347,331.76 ± 91,933.58 | 263,698.08 ± 49,573.01 | 299,899.63 ± 57,695.8 | 200,315.81 ± 68,510.44 |
2-oxoglutarate | 3755.05 (3476.57–4032.21) | 3968.36 (3587–4421.18) | 3984.51 (3393.35–4323.3) | 4290.49 (3868.34–5168.94) |
Acetoacetate | 2473.04 (1277.63–4600.98) | 18,926.55 (7189.31–30,038.77) | 4166.43 (2374.53–7277.45) | 9580.02 (6992.68–30,978.53) |
Succinate | 722.6 (588.57–1221.9) | 1725.48 (1325.02–2012.26) | 515.06 (297.41–1150.89) | 1838.29 (1344.81–2370.32) |
3-hydroxybutyrate | 14,338.64 (3125–53,089.27) | 162,982.81 (48,176.41–401,805.24) | 3125 (3125–23,132.58) | 146,012.84 (46,441.35–303,043.91) |
Glutarate | 636.45 (548.76–906.39) | 530.86 (480.5–618.66) | 664.43 (528.85–922.1) | 526.83 (479.83–668.31) |
Fresenius ACF 3A5 | Fresenius Smartbag CA 211.5 | |
---|---|---|
Sodium (mmol/L) | 140 | 138 |
Potassium (mmol/L) | 2 | 2 |
Calcium (mmol/mL) | 1.5 | 1.5 |
Magnesium (mmol/mL) | 0.5 | 0.5 |
Chloride (mmol/mL) | 106 | 109 |
Acetate (mmol/L) | 4 | - |
Citrate (mmol/L) | - | 1 |
Glucose (g/L) | 1 | 1 |
Bicarbonate (mmol/L) | 35 | 32 |
In-use dilution | 1 + 44 | 1 + 44 |
Metabolite | Chemical Formula | Molecular Mass (g/mol) | Biochemical Class | Main Metabolic Pathways |
---|---|---|---|---|
Acetylcarnitine | C9H17NO4 | 203.236 | Fatty acid esters | Oxidation of fatty acids |
Fumarate | C4H4O4 | 116.072 | Dicarboxylic acids and derivatives | TCA cycle (2nd carbon oxidation), electron transport chain |
Citrate | C6H8O7 | 189.1 | Tricarboxylic acids and derivatives | TCA cycle (1st carbon oxidation), transfer of acetyl groups into mitochondria |
Isocitrate | C6H8O7 | 189.1 | Tricarboxylic acids and derivatives | TCA cycle (1st carbon oxidation) |
Myo-inositol | C6H12O6 | 180.16 | Alcohols and polyols | Inositol phosphate metabolism, secondary messenger in signal transduction pathways |
Glutamate | C5H9NO4 | 147.13 | Amino acids, peptides, and analogues | Aminoacidic metabolism |
Pyruvate | C3H4O3 | 88.06 | Alpha-keto acids and derivatives | Glycolysis, gluconeogenesis, lipogenesis |
Malate | C4H6O5 | 134.08 | Beta hydroxy acids and derivatives | TCA cycle (2nd carbon oxidation), gluconeogenesis, pyruvate metabolism |
Glycerol | C3H8O3 | 92.09 | Carbohydrates and carbohydrate conjugates | Triglyceride metabolism |
Lactate | C3H6O3 | 90.08 | Alpha hydroxy acids and derivatives | Gluconeogenesis, pyruvate metabolism |
2-oxoglutarate | C5H6O5 | 146.11 | Gamma-keto acids and derivatives | TCA cycle (1st carbon oxidation), aminoacidic metabolism |
Acetoacetate | C4H6O3 | 101.08 | Short-chain keto acids and derivatives | Ketone body metabolism, fatty acid biosynthesis |
Succinate | C4H6O4 | 118.09 | Dicarboxylic acids and derivatives | TCA cycle (2nd carbon oxidation), electron transport chain |
3-hydroxybutyrate | C4H8O3 | 103.1 | Beta hydroxy acids and derivatives | Ketone body metabolism, fatty acid biosynthesis |
Glutarate | C5H8O4 | 147.13 | Dicarboxylic acids and derivatives | Aminoacidic metabolism |
TCA: Krebs tricarboxylic acid. |
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Broseta, J.J.; Roca, M.; Rodríguez-Espinosa, D.; López-Romero, L.C.; Gómez-Bori, A.; Cuadrado-Payán, E.; Devesa-Such, R.; Soldevila, A.; Bea-Granell, S.; Sánchez-Pérez, P.; et al. Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach. Int. J. Mol. Sci. 2022, 23, 11693. https://doi.org/10.3390/ijms231911693
Broseta JJ, Roca M, Rodríguez-Espinosa D, López-Romero LC, Gómez-Bori A, Cuadrado-Payán E, Devesa-Such R, Soldevila A, Bea-Granell S, Sánchez-Pérez P, et al. Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach. International Journal of Molecular Sciences. 2022; 23(19):11693. https://doi.org/10.3390/ijms231911693
Chicago/Turabian StyleBroseta, José Jesús, Marta Roca, Diana Rodríguez-Espinosa, Luis Carlos López-Romero, Aina Gómez-Bori, Elena Cuadrado-Payán, Ramón Devesa-Such, Amparo Soldevila, Sergio Bea-Granell, Pilar Sánchez-Pérez, and et al. 2022. "Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach" International Journal of Molecular Sciences 23, no. 19: 11693. https://doi.org/10.3390/ijms231911693