Sodium barbital is a slow reversible inactivator of rabbit-muscle creatine kinase.
As a depressant of the central nervous system, the clinical effect of sodium barbital has been extensively studied. Here we report on sodium barbital as an inhibitor of rabbit-muscle creatine kinase (CK), which plays a significant role in energy homeostasis in the muscles. Although sodium barbital gradually inhibits the activity of CK with increased concentration, the inhibition effect can be completely reversed by dilution, indicating that the inactivation process is reversible. Detailed kinetics analysis, according to a previously presented theory, indicates that sodium barbital functions as a non complexing inhibitor, and its inhibition effect on CK is a slow reversible inactivation. In this study, a kinetic model of the substrate reaction is presented, and the microscopic rate constants for the reaction of sodium barbital with the free enzyme and the enzyme-substrate complexes are determined. Kinetic analysis reveals that sodium barbital might compete with both creatine and ATP, but mainly with creatine, to inhibit the activity of CK. The results suggest that CK might be a target for sodium barbital in vivo.
Shi
Feng
F
College of Life Sciences, Zhejiang University, Hangzhou, PR China.
Zhao
Tong-Jin
TJ
He
Hua-Wei
HW
Li
Jie
J
Zeng
Xian-Gang
XG
Zhou
Hai-Meng
HM
Wu
Ping
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001462:Barbital / Q000494:pharmacology*; D003401:Creatine / Q000378:metabolism; D052283:Creatine Kinase, MM Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D011817:Rabbits
D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D001462:Barbital; D000255:Adenosine Triphosphate; D052283:Creatine Kinase, MM Form; D003401:Creatine