Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion—Revisiting the Warburg Effect
Abstract
:Simple Summary
Abstract
1. Introduction
2. Glucose and Lactate Metabolism in Normal Body Tissues
Sample | Metabolite | Concentration (mM) | Ratio | References | |||
---|---|---|---|---|---|---|---|
Means | Range 1 | SD | n 2 | ||||
Blood | lactate (resting) | 1.597 | 0.800–3.500 | 0.738 | 10 | [lac]/[pyr] 22.0 | [42,43,44,45,46,47,48,49,50] |
pyruvate (resting) | 0.073 | 0.032–0.120 | 0.027 | 7 | [46,47,48,49,50,51,52] | ||
lactate (exercising) | 6.200 | 5.500–7.500 | 0.748 | 5 | - | [45,47,49,50,52] | |
RBC | lactate | 1.021 | 0.200–1.870 | 0.454 | 7 | [lac]/[pyr] 16.7 | [43,44,46,53,54,55] |
pyruvate | 0.061 | 0.043–0.083 | 0.013 | 5 | [46,53,54,55] | ||
NAD+ | 0.051 | 0.040–0.062 | 0.011 | 2 | [NAD+]/[NADH] 1.9 | [46,55] | |
NADH | 0.027 | 0.027 | 0.000 | 1 | [55] | ||
Tumor cell line | lactate | 13.033 | 2.000–35.525 | 10.905 | 12 | [lac]/[pyr] 17.8 | [39,56,57] |
pyruvate | 0.733 | 0.130–5.880 | 1.326 | 19 | [56,57,58,59,60] | ||
NAD+ | 0.486 | 0.470–0.502 | 0.016 | 2 | [NAD+]/[NADH] 6.9 | [58,59] | |
NADH | 0.070 | 0.065–0.075 | 0.005 | 2 | [58,59] |
3. Key Enzymes and Metabolites at the Pyruvate Junction
4. Switching to the Tumor Metabolic Phenotype
5. Maintaining the Redox Balance under the Forced Growth Conditions in Cancer Cells
6. Conclusions
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
References
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Enzyme | Subtype | Cell Type | Normal/ Tumor | Substrate | Allosteric Effector 1 | KM (mM) Means | KM (mM) Range 2 | KM (mM)SD | n 3 | References |
---|---|---|---|---|---|---|---|---|---|---|
PK | M1 | muscle | normal | PEP | - | 0.057 | 0.032–0.085 | 0.019 | 7 | [76,77,78,79,80,81,82] |
M2 | many | normal | PEP | - | 0.421 | 0.140–0.860 | 0.223 | 8 | [77,78,79,81,82,83,84,85] | |
tumor | PEP | - | 0.648 | 0.130–2.100 | 0.542 | 9 | [57,86,87] | |||
normal | PEP | F1,6BP | 0.064 | 0.030–0.100 | 0.026 | 4 | [77,78,85,88] | |||
tumor | PEP | F1,6BP | 0.103 | 0.030–0.170 | 0.057 | 3 | [57,86,87] | |||
L, R | liver, RBC | normal | PEP | - | 0.736 | 0.500–1.100 | 0.178 | 8 | [75,78,79,81,88,89] | |
normal | PEP | F1,6BP | 0.073 | 0.060–0.090 | 0.013 | 3 | [75,81] | |||
PDH | normal | pyruvate | - | 0.020 | 0.005–0.043 | 0.011 | 9 | [90,91,92,93,94,95,96,97] | ||
PC | normal | pyruvate | - | 0.265 | 0.230–0.300 | 0.035 | 2 | [98,99] | ||
GPT/ ALT | normal | pyruvate | - | 2.800 | 0.070–12.50 | 4.858 | 5 | [100,101,102,103,104] | ||
normal | Ala | - | 22.003 | 10.12–34.00 | 7.735 | 8 | [100,101,102,103,104,105,106,107] | |||
normal | Glu | - | 9.830 | 3.22–15.00 | 4.568 | 4 | [101,102,103,107] | |||
normal | 2-OG | - | 0.523 | 0.100–1.100 | 0.356 | 6 | [100,101,102,103,105,106] | |||
LDH | 1 (B, H) | heart, (RBC) | normal | pyruvate | - | 0.100 | 0.034–0.243 | 0.063 | 17 | [30,32,106,108,109,110,111,112,113,114,115,116,117,118,119,120] |
normal | lactate | - | 5.916 | 2.000–9.690 | 2.911 | 8 | [30,32,108,109,115,121,122] | |||
normal | NADH | - | 0.038 | 0.014–0.069 | 0.023 | 3 | [32,112,116] | |||
normal | NAD+ | - | 0.123 | 0.075–0.170 | 0.039 | 3 | [30,109,121] | |||
5 (A, M) | liver, muscle, (heart) (RBC) | normal | pyruvate | - | 0.288 | 0.095–0.630 | 0.173 | 12 | [30,32,109,111,113,115,117,118,120,123,124] | |
normal 4 | pyruvate | - | 0.630 | - | - | 1 4 | [124] | |||
tumor 4 | pyruvate | - | 0.780 | - | - | 1 4 | [124] | |||
normal | lactate | - | 15.940 | 6.880–40.000 | 7.759 | 15 | [30,32,109,115,121,122,124,125] | |||
normal 4 | lactate | - | 10.730 | - | - | 1 4 | [124] | |||
tumor 4 | lactate | - | 21.780 | - | - | 1 4 | [124] | |||
normal | NADH | - | 0.173 | 0.016–0.330 | 0.157 | 2 | [32,124] | |||
normal 4 | NADH | - | 0.300 | - | - | 1 4 | [124] | |||
tumor 4 | NADH | - | 0.330 | - | - | 1 4 | [124] | |||
normal | NAD+ | - | 0.337 | 0.220–0.500 | 0.119 | 3 | [109,121,124] | |||
normal | NAD+ | - | 0.500 | 0.220–0.500 | 0.119 | 3 | [124] | |||
tumor | NAD+ | 0.990 | - | - | 1 | [124] |
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Niepmann, M. Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion—Revisiting the Warburg Effect. Cancers 2024, 16, 2290. https://doi.org/10.3390/cancers16132290
Niepmann M. Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion—Revisiting the Warburg Effect. Cancers. 2024; 16(13):2290. https://doi.org/10.3390/cancers16132290
Chicago/Turabian StyleNiepmann, Michael. 2024. "Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion—Revisiting the Warburg Effect" Cancers 16, no. 13: 2290. https://doi.org/10.3390/cancers16132290
APA StyleNiepmann, M. (2024). Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion—Revisiting the Warburg Effect. Cancers, 16(13), 2290. https://doi.org/10.3390/cancers16132290