TABLE 1

Substrate sensitivities of human and mouse NaCT

Responses of the various substrates were normalized to control responses to 3 mM and 30 μM citrate human and mouse NaCT, respectively. Data are presented as means ± S.E. and means (95% confidence intervals). In the fields in which no values are given (indicated with dashes), the responses to the substrate were either too small to fit a curve to the data, or the concentration-response curves did not saturate at the highest concentrations of the substrates tested. Conservative estimates for “fold difference” values were calculated by using the upper value for the 95% confidence interval of the mouse EC50 and the lower value for the 95% confidence interval for the human EC50; therefore, the true “fold difference” is likely even greater than the reported values. All substrates tested were significantly more potent on mouse NaCT compared with human NaCT (t test, P < 0.001).

CompoundHuman NaCTMouse NaCTFold Difference
EC50EmaxnHnEC50EmaxnHn
mM%μM%
Citrate3.5 (3.3–3.7)217 ± 31.27 ± 0.0447.2 (6.5–8.0)116 ± 21.24 ± 0.063>400
Oxaloacetate1.6 (0.3–9.0)19 ± 40.70 ± 0.26312 (9–18)93 ± 41.02 ± 0.133>20
Malate6.6 (6.2–7.1)153 ± 32.18 ± 0.06322 (17–29)102 ± 41.03 ± 0.103>200
α-Ketoglutarate18.0 (3.9–84)334 ± 1191.11 ± 0.2833
Succinate9.3 (7.4–12)92 ± 41.01 ± 0.0535.5 (3.3–9.2)80 ± 51.10 ± 0.253>800
Fumarate20 (19-21)108 ± 11.01 ± 0.02326 (14–46)119 ± 121.24 ± 0.313>400
Isocitrate10.46 ± 2334 (6–180)21 ± 71.55 ± 1.483>60