ABSTRACT

I. Introduction ...................................................................................................................... 861

II. Theory .............................................................................................................................. 862

III. Examples .......................................................................................................................... 866

A. Cytochrome P450..................................................................................................... 866

B. The Aromatic Amino Acid Hydroxylases............................................................... 868

C. Dopamine b-Monooxygenase.................................................................................. 870

IV. Conclusion........................................................................................................................ 871

References..................................................................................................................................... 871

As discussed elsewhere in this volume, substitution with a heavier isotope of an atom in the

substrate for an enzyme-catalyzed reaction will not necessarily result in a detectable change in

either the rate of product formation in a single assay or on the V

and V/K values determined from

more complete kinetic analyses. Expression of intrinsic isotope effects on V

values can be

masked by slower chemical steps steps which are not isotope-sensitive and by slow product release,

while effects on V/K values can be masked by high commitments to catalysis.