A unified theory of enzyme kinetics based upon the systematic analysis of the variations of k(cat), K(M), and k(cat)/K(M) and the relevant DeltaG(0 not equal) values-possible implications in chemotherapy and biotechnology.
To elucidate the kinetic properties of critical enzymatic situations that have previously escaped classification, we performed a systematic analysis of all the possible variations of the kinetic constants k(cat,) K(M,) and k(sp) = k(cat)/K(M,) encompassing all aspects of enzymology. The equation gives a total of thirteen theoretically possible cases, comprising the reference case plus 12 different sets of variations, which can be divided into six principal cases and six specular ones. The six relevant cases are examined individually in the context of each of the main chapters of enzymology, i.e. as regards mechanism of action, specificity of substrate and isoenzyme, reversible and irreversible inhibition, and mutation of residues (enzyme evolution and enzyme engineering). Some critical cases where k(sp) does not hold as a specificity index are classified for the first time. Interestingly, the six possible cases correspond to the five known cases of reversible inhibition (competitive, non-competitive, incompetitive, mixed competitive/non-competitive, and mixed incompetitive/non-competitive) plus an additional case of biphasic nature (activation-inhibition), which is crucial for a full understanding of specificity and which leads us to propose some modification to the definition of enzyme specificity. The systematic approach to enzymology outlined herein could find practical applications in various sectors of biotechnology, including chemotherapy.
Bauer
C
C
Department of Physiology and Biochemistry, Biochemistry Unit, University of Pisa, via S. Maria 55, I-56126 Pisa, Italy.
Osman
A M
AM
Cercignani
G
G
Gialluca
N
N
Paolini
M
M
D001667:Binding, Competitive; D001709:Biotechnology; D004358:Drug Therapy / Q000379:methods; D004734:Energy Metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D013379:Substrate Specificity
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D004798:Enzymes