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KINETIC ISOTOPE EFFECTS OF DEUTERIUM OXIDE ON SEVERAL /cap alpha/- CHYMOTRYPSIN-CATALYZED REACTIONS

Journal Article · · Journal of the American Chemical Society (U.S.)
DOI:https://doi.org/10.1021/ja00872a022· OSTI ID:4820169

The kinetics of several reactions catalyzed by alpha chymotrypsin were determined in D/sub 2/O as solvent, and the results were compared with the kinetics of the same reactions in H/sub 2/O as solvent. By a suitable choice of substrates it was possible to estimate the effect of D/sub 2/O on the binding of the substrate to the enzyme, acylation of the enzyme, and deacylation of the acyl- enzyme intermediate. The substrate p-nitrophenyl trimethylicetate was used for studying the acylation reaction, and trans-cinnimoyl- alpha -chymotrypsin and trimethylacetyl- alpha -chymotrypsin were used for studying the deacylation reaction. A sizable isotope effect was observed for both the acylation and deacylation reactions L-tryptophan methyl ester were also compared in D/sub 2/O and H/sub 2/O and it was observed that at high substrate concentrations the limiting rate constant is greater in H/sub 2/O than in D/sub 2/O by a factor of 2.83. The results indicate a ratedetermining proton transfer in the catalytic steps of the enzymatic reaction. (auth)

Research Organization:
Illinois Inst. of Tech., Chicago
Sponsoring Organization:
USDOE
NSA Number:
NSA-16-026999
OSTI ID:
4820169
Journal Information:
Journal of the American Chemical Society (U.S.), Journal Name: Journal of the American Chemical Society (U.S.) Vol. Vol: 84; ISSN JACSA
Country of Publication:
Country unknown/Code not available
Language:
English