Holtzman D, Offutt M, Tsuji M, Neuringer L J, Jacobs D
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA 02115.
J Cereb Blood Flow Metab. 1993 Jan;13(1):153-61. doi: 10.1038/jcbfm.1993.18.
Brain creatine kinase (CK)-catalyzed phosphorus flux from phosphocreatine (PC) to ATP was measured in vivo in young adult mice made reversibly hypoxic by injection of cyanide. Phosphorus spectra and saturation transfer measurements of CK-catalyzed flux were acquired using a high-field (8.45 T) nuclear magnetic resonance (NMR) spectrometer. After low cyanide doses (1-3 mg/kg of body weight), there were no measurable changes in brain pH or in concentrations of PC, the nucleoside triphosphates (including ATP), and Pi. The CK-catalyzed phosphorus flux increased about 75% after the low cyanide dose. Higher doses (4-6 mg/kg) produced a transient 30-40% decrease in PC concentration, doubling of Pi, and a 0.2 unit decrease in pH. The CK-catalyzed phosphorus flux decreased 50-80% after the higher cyanide doses. This decrease in phosphorus flux was present long after reactant concentrations returned to precyanide values. It is proposed that the increase in brain CK-catalyzed phosphorus flux with the lower cyanide doses is due to an increase in ADP concentration. The large, prolonged decrease in CK-catalyzed reaction rate in the moderately poisoned brain may be due to loss of activity of the mitochondrial CK isoform.
通过注射氰化物使成年小鼠可逆性缺氧，在此条件下对其体内脑肌酸激酶（CK）催化的磷酸肌酸（PC）向ATP的磷通量进行了测量。使用高场（8.45 T）核磁共振（NMR）光谱仪获取了CK催化通量的磷光谱和饱和转移测量结果。低剂量氰化物（1 - 3 mg/kg体重）注射后，脑pH值以及PC、核苷三磷酸（包括ATP）和无机磷酸（Pi）的浓度均无明显变化。低剂量氰化物注射后，CK催化的磷通量增加了约75%。较高剂量（4 - 6 mg/kg）导致PC浓度短暂下降30 - 40%，Pi浓度翻倍，pH值下降0.2个单位。较高剂量氰化物注射后，CK催化的磷通量下降了50 - 80%。在反应物浓度恢复到氰化物注射前的值后很长时间，这种磷通量的下降仍然存在。研究表明，低剂量氰化物导致脑CK催化的磷通量增加是由于ADP浓度升高所致。中度中毒的大脑中CK催化反应速率大幅且持续下降，可能是由于线粒体CK同工酶活性丧失所致。
