Volatile anesthetics-induced activation phenomena of alpha-chymotrypsin-catalyzed hydrolysis.
The rates of hydrolysis of p-nitrophenyl acetate (pNPA), p-nitrophenyl propionate (pNPP), p-nitrophenyl butanate (pNPB), and p-nitrophenyl valerate (pNPV) catalyzed by alpha-chymotrypsin (alpha-CHT) were measured with and without volatile anesthetics at 25.0 degrees C. Halothane activated the hydrolysis of pNPA and pNPP, meanwhile inhibited that of pNPB and pNPV. The activation phenomena were explained by the existence of a 1:1 enzyme-anesthetics complex and the opening of an activated pathway. The rate constant of pNPA hydrolysis catalyzed by alpha-CHT of the activated pathway kA by halothane was 0.269 s-1, whereas that of the normal pathway was k0 0.093 s-1. The free energy of activation was stabilized at 0.64 kcal/mol by halothane. The mechanisms of the activation and inhibition are discussed in terms of the molecular size of the substrate and anesthetics.
Seto
T
T
Department of Anesthesiology, Osaka University Medical School, Japan.
Makimoto
S
S
Mashimo
T
T
Yoshiya
I
I
Taniguchi
Y
Y
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002918:Chymotrypsin / Q000378:metabolism*; D004737:Enflurane / Q000494:pharmacology; D004789:Enzyme Activation; D006221:Halothane / Q000494:pharmacology; D006868:Hydrolysis; D007530:Isoflurane / Q000494:pharmacology; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D010179:Pancreas / Q000201:enzymology; D013379:Substrate Specificity
D000777:Anesthetics; D004737:Enflurane; D007530:Isoflurane; D002918:Chymotrypsin; D006221:Halothane