Creatine kinase-catalyzed reaction rate in the cyanide-poisoned mouse brain.

Creatine kinase-catalyzed reaction rate in the cyanide-poisoned mouse brain.
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氰化物中毒小鼠大脑中肌酸激酶催化的反应率。

DOI:
10.1038/jcbfm.1993.18
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发表时间:
1993
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子:
--
通讯作者:
Jacobs,D
Jacobs,D
中科院分区:
--
文献类型:
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作者:
Holtzman,D;Offutt,M;Tsuji,M;Neuringer,LJ;Jacobs,D

文献摘要

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用氰化物致小鼠可逆性缺氧,在体内测定了脑肌酸激酶(CK)催化的磷酸肌酸(PC)向ATP的磷通量。磷光谱和饱和转移测量CK催化通量获得使用高场(8.45 T)核磁共振(NMR)光谱仪。在低氰化物剂量(1-3 mg/kg体重)后,脑pH或PC、核苷三磷酸(包括ATP)和Pi的浓度没有可测量的变化。在低氰化物剂量后,CK催化的磷通量增加约75%。较高剂量(4-6 mg/kg)导致PC浓度一过性降低30-40%,Pi加倍,pH值降低0.2个单位。较高氰化物剂量后,CK催化的磷通量降低50-80%。在反应物浓度恢复到氰化物前值后很长时间,磷通量才出现这种下降。有人提出,增加脑CK催化磷通量与较低的氰化物剂量是由于ADP浓度的增加。中度中毒大脑中CK催化反应速率的大幅、长期下降可能是由于线粒体CK亚型活性丧失所致。
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.