Table 2.
Expression levels of enzymes involved in the interconversion of isotopologues detected in the fluxomic analysis. Enzyme levels were determined by proteomic analysis and subjected to Log2 normalization. *p ≤ 0.05 and **p ≤ 0.01 indicate significant differences between DSC untreated vs. CC untreated; #p ≤ 0.05 indicates significant differences between CC + AOAA vs. CC untreated or DSC + AOAA vs. DSC untreated.
| Enzyme | Pathway | CC | CC + AOAA | DSC | DSC + AOAA |
|---|---|---|---|---|---|
| Hexokinase 1 | Glycolysis | 13.55 ± 0.03 | 13.54 ± 0.03 | 13.53 ± 0.05 | 13.52 ± 0.05 |
| Hexokinase 2 | Glycolysis | 11.86 ± 0.05 | 11.70 ± 0.06 | 11.76 ± 0.05 | 11.73 ± 0.06 |
| glucose-6-phosphate isomerase | Glycolysis | 13.57 ± 0.18 | 13.58 ± 0.16 | 13.70 ± 0.10 | 13.63 ± 0.12 |
| Phosphofructokinase-1, muscle type | Glycolysis | 11.36 ± 0.04 | 11.36 ± 0.03 | 11.53 ± 0.03** | 11.54 ± 0.02 |
| Phosphofructokinase-1, liver type | Glycolysis | 12.46 ± 0.04 | 12.44 ± 0.03 | 12.78 ± 0.04** | 11.87 ± 0.03# |
| Fructose-bisphosphate aldolase | Glycolysis | 10.98 ± 0.09 | 10.93 ± 0.11 | 10.83 ± 0.10 | 10.81 ± 0.09 |
| Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) | Glycolysis | 12.59 ± 0.09 | 12.42 ± 0.04 | 12.31 ± 0.07* | 12.27 ± 0.05 |
| 3-phosphoglycerate kinase (3-PGK) | Glycolysis | 14.38 ± 0.06 | 14.38 ± 0.07 | 14.41 ± 0.07 | 14.39 ± 0.06 |
| Phosphoglycerate mutase (PGM) | Glycolysis | 13.43 ± 0.04 | 13.42 ± 0.03 | 13.56 ± 0.03* | 13.53 ± 0.03 |
| Enolase 1 (ENO-1) | Glycolysis | 15.73 ± 0.06 | 15.67 ± 0.03 | 15.69 ± 0.08 | 15.65 ± 0.04 |
| Enolase 2 (ENO-2) | Glycolysis | 11.39 ± 0.06 | 11.30 ± 0.07 | 11.37 ± 0.06 | 11.40 ± 0.05 |
| Pyruvate kinase M1/M2 | Glycolysis | 15.69 ± 0.04 | 15.68 ± 0.03 | 15.74 ± 0.04 | 15.75 ± 0.04 |
| Lactate dehydrogenase (LDH) A | Glycolysis | 14.90 ± 0.04 | 14.88 ± 0.04 | 14.96 ± 0.05 | 14.92 ± 0.05 |
| Lactate dehydrogenase (LDH) B | Glycolysis | 13.48 ± 0.04 | 13.42 ± 0.05 | 13.38 ± 0.06 | 13.35 ± 0.03 |
| Pyruvate dehydrogenase E1 subunit alpha | Glycolysis, Krebs cycle | 11.40 ± 0.03 | 11.39 ± 0.03 | 11.34 ± 0.03 | 11.33 ± 0.02 |
| Pyruvate dehydrogenase E1 subunit beta | Glycolysis, Krebs cycle | 11.82 ± 0.04 | 11.78 ± 0.02 | 11.81 ± 0.03 | 11.80 ± 0.03 |
| Pyruvate dehydrogenase (PDH) complex component X | Krebs cycle | 10.39 ± 0.06 | 10.40 ± 0.05 | 10.36 ± 0.05 | 10.35 ± 0.05 |
| Citrate synthase | Krebs cycle | 12.60 ± 0.03 | 12.58 ± 0.03 | 12.59 ± 0.05 | 12.57 ± 0.05 |
| Aconitase 1 | Krebs cycle | 12.47 ± 0.08 | 12.41 ± 0.07 | 12.43 ± 0.06 | 12.45 ± 0.06 |
| Aconitase 2 | Krebs cycle | 12.51 ± 0.03 | 12.52 ± 0.02 | 12.47 ± 0.05 | 12.45 ± 0.05 |
| Isocitrate dehydrogenase (ICDH) 1 | Krebs cycle | 13.13 ± 0.06 | 13.13 ± 0.06 | 13.33 ± 0.07* | 13.27 ± 0.06# |
| Isocitrate dehydrogenase (ICDH) 2 | Krebs cycle | 12.53 ± 0.09 | 12.54 ± 0.09 | 12.64 ± 0.09 | 12.70 ± 0.08 |
| α-ketoglutarate dehydrogenase (α−KGDH) | Krebs cycle | 12.39 ± 0.05 | 12.36 ± 0.06 | 12.45 ± 0.04 | 12.44 ± 0.05 |
| Succinyl-CoA synthetase (S-CoAS) - GDP-forming subunit beta | Krebs cycle | 11.02 ± 0.04 | 10.98 ± 0.03 | 10.98 ± 0.04 | 11.01 ± 0.05 |
| Succinyl-CoA synthetase (S-CoAS) - GDP/ADP-forming subunit alpha | Krebs cycle | 12.42 ± 0.03 | 12.42 ± 0.04 | 12.38 ± 0.04 | 12.37 ± 0.03 |
| Succinate dehydrogenase (SDH) complex flavoprotein subunit A | Krebs cycle | 11.72 ± 0.02 | 11.69 ± 0.04 | 11.78 ± 0.05 | 11.77 ± 0.04 |
| Succinate dehydrogenase (SDH) complex subunit B | Krebs cycle | 11.36 ± 0.02 | 11.30 ± 0.04 | 11.34 ± 0.03 | 11.41 ± 0.04 |
| Succinate dehydrogenase (SDH) complex subunit C | Krebs cycle | 7.06 ± 0.03 | 7.13 ± 0.05 | 7.17 ± 0.05 | 7.18 ± 0.03 |
| Fumarase | Krebs cycle | 12.61 ± 0.03 | 12.58 ± 0.04 | 12.59 ± 0.03 | 12.55 ± 0.02 |
| Malate dehydrogenase 1 (MDH-1) | Krebs cycle | 13.03 ± 0.01 | 13.04 ± 0.03 | 13.18 ± 0.01** | 13.16 ± 0.03 |
| Malate dehydrogenase 2 (MDH-2) | Krebs cycle | 13.73 ± 0.05 | 13.67 ± 0.04 | 13.79 ± 0.04 | 13.74 ± 0.05 |
| Glucose-6-phosphate dehydrogenase (G6PDH) | PPP | 13.35 ± 0.04 | 13.31 ± 0.08 | 13.30 ± 0.04 | 13.33 ± 0.03 |
| 6-phosphogluconate dehydrogenase (6-PGDH) | PPP | 13.47 ± 0.05 | 13.45 ± 0.05 | 13.47 ± 0.09 | 13.42 ± 0.08 |
| Glycerol-3-phosphate dehydrogenase (G3PDH) | PPP | 12.59 ± 0.09 | 12.42 ± 0.04 | 12.31 ± 0.07 | 12.27 ± 0.05 |
| Glucolactonase | PPP | 12.17 ± 0.05 | 12.17 ± 0.04 | 12.31 ± 0.03* | 12.32 ± 0.03 |
| Transketolase | PPP | 13.97 ± 0.05 | 13.95 ± 0.05 | 13.92 ± 0.04 | 13.87 ± 0.04 |
| Phosphoglycerate dehydrogenase | Serine synthesis | 13.17 ± 0.08 | 13.19 ± 0.08 | 13.18 ± 0.09 | 13.17 ± 0.09 |
| Phosphoserine phosphatase (PDPH) | Serine synthesis | 10.11 ± 0.07 | 10.10 ± 0.09 | 10.16 ± 0.13 | 10.06 ± 0.10 |
| ATP citrate lyase (ACLY) | Fatty acid synthesis | 14.33 ± 0.04 | 14.33 ± 0.04 | 14.49 ± 0.04 | 14.49 ± 0.03 |
| Acetyl-CoA carboxylase (ACC) | Fatty acid synthesis | 11.46 ± 0.03 | 11.47 ± 0.03 | 11.49 ± 0.04 | 11.51 ± 0.04 |
| Fatty acid synthase (FAS) | Fatty acid synthesis | 14.27 ± 0.05 | 14.28 ± 0.05 | 14.27 ± 0.04 | 14.29 ± 0.04 |
| Phosphoribosyl pyrophosphate synthetase (PRPS) 1 | NAD+ synthesis | 12.55 ± 0.12 | 12.50 ± 0.12 | 12.60 ± 0.09 | 12.55 ± 0.11 |
| Phosphoribosyl pyrophosphate synthetase (PRPS) 2 | NAD+ synthesis | 9.96 ± 0.07 | 9.94 ± 0.06 | 9.87 ± 0.07 | 9.82 ± 0.07 |