Table 3. Fluxes through pathways of 5 and 1 mmol/L [3-13C]glutamine metabolism in brain slices of wild-type (WT) and glutaminase-deficient (GLS1+/−) mice.
Experimental condition |
Flux (μmol of C3 units/g dry
weight per hour) |
|||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PAG | GS | Uni Glu → αKG | Uni αKG → Glu | GAD | SucDH | MDH | ME | AspAT | PK | AlaAT | PDH | PC | CS | |
5 mmol/L [3- 13 C]glutamine | ||||||||||||||
WT mice (n=8) | 101.1±6.2 | 14.0±2.3 | 104.4±5.6 | 15.9±2.3 | 5.1±0.5 | 257.6±12.1 | 154.7±18.7 | 102.9±11.6 | 29.3±1.9 | 5.8±0.2 | 2.0±0.2 | 85.6±4.1 | 36.5±13.0 | 162.0±8.4 |
GLS1+/− mice (n=8) | 80.3±5.6a | 10.1±1.4 | 89.4±5.5 | 11.9±1.6 | 4.4±0.3 | 223.4±9.6a | 119.0±20.5 | 104.4±17.3 | 27.2±2.2 | 6.0±0.3 | 2.0±0.3 | 77.5±3.6 | 47.3±17.6 | 139.2±5.8a |
1 mmol/L [3- 13 C]glutamine | ||||||||||||||
WT mice (n=8) | 40.7±1.0 | 4.7±1.6 | 65.3±1.9 | 7.2±06 | 4.2±0.4 | 182.2±8.6 | 110.9±4.7 | 71.3±3.9 | 22.6±0.8 | 5.7±0.2 | 0.9±0.1 | 61.6±3.4 | 28.3±1.2 | 116.6±6.4 |
GLS1+/− mice (n=8) | 32.4±1.3a | 6.4±1.4 | 57.0±1.2a | 8.4±1.0 | 3.3±0.7 | 153.4±5.2a | 91.9±2.5a | 61.5±2.7 | 20.8±0.5 | 5.4±0.1 | 0.2±0.2a | 54.8±2.0 | 27.2±0.7 | 98.4±3.6a |
PAG, phosphate-activated glutaminase; GS, glutamine synthetase; Uni Glu → αKG, unidirectional flux from glutamate to α-ketoglutarate; Uni αKG → Glu, unidirectional flux from α-ketoglutarate to glutamate; GAD, glutamic acid decarboxylase; SucDH, succinate dehydrogenase; MDH, malate dehydrogenase; ME, malic enzyme; AspAT, aspartate aminotransferase; PK, pyruvate kinase; AlaAT, alanine aminotransferase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; CS, citrate synthase.
Brain slices were incubated for 1 hour with 5 or 1 mmol/L [3-13C]glutamine. Results (in μmol of C3 units/g dry weight per hour) are presented as means±s.e.m. for eight experiments. Statistical difference was measured by the unpaired Student's t-test and P<0.05 was considered statistically significant.
Different from WT mice.