Monoamine oxidase catalysis

Kim, J.-M., Bogdon, M. A., and Mariano, P. S., 1993, Mechanistic analysis of the 3-methyllumiflavin-promoted oxidative deamination of benzylamineoa potential model for monoamine oxidase catalysis, J. Am. Chem. Soc. 115 10591910595. 

Competitive inhibitors bind to specific groups in the enzyme active site to form an enzyme-inhibitor complex. The inhibitor and substrate compete for the same site, so that the substrate is prevented from binding. This is usually because the substrate and inhibitor share considerable stmctural similarity. Catalysis is diminished because a lower proportion of molecules have a bound substrate. Inhibition can be relieved by increasing the concentration of substrate. Some simple examples are shown below. Thus, sulfanilamide is an inhibitor of the enzyme that incorporates j9-aminobenzoic acid into folic acid, and has antibacterial properties by restricting folic acid biosynthesis in the bacterium (see Box 11.13). Some phenylethylamine derivatives, e.g. phenelzine, provide useful antidepressant drags by inhibiting the enzyme monoamine oxidase. The cA-isomer maleic acid is a powerful inhibitor of the enzyme that utilizes the trans-isomer fumaric acid in the Krebs cycle. 

Edmondson, D. E., 1995, Aminium cation radical mechanism proposed for monoamine oxidase B catalysis are there alternatives , Xenobiotica 25 7359753. 

Suicide inhibitors, or mechanism-based inhibitors are modified substrates that provide the most specific means to modify an enzyme active site. The inhibitor binds to the enzyme as a substrate and is initially processed by the normal catalytic mechanism. The mechanism of catalysis then generates a chemically reactive intermediate that inactivates the enzyme through covalent modification. The fact that the enzyme participates in its own irreversible inhibition strongly suggests that the covalently modified group on the enzyme is catalytically vital. One example of such an inhibitor is N,N-dimethylpropargylamine. A flavin prosthetic group of monoamine oxidase... 

CONTENTS Preface, Patrick. Mariano. Hole and Electron Transfer Catalyzed Pericyclic Reactions. Nathan L. Baufd. Mechanisms and Catalysis In Electron Transfer Chemistry of Redox Coenzyme Analogues, Shunichi Fukuaumi. Electron T ransfer Chemistry of Monoamine Oxidase. Richard B. Silverman. Photol-yase. DNA Repair by Photoinduced Electron Transfer, Aziz San-car. Index. R T7... 

The animal diamine oxidase is inhibited by cyanide and other carbonyl reagents. In contrast to liver monoamine oxidase, diamine oxidase is not sensitive to p-chloromercuribenzoate or other SH reagents. Iso-nicotinoyl hydrazide is a potent inhibitor of diamine oxidase. The chemical basis for the inhibitions are not known. It has been suggested that the bacterial enzymes contain flavins, but there is no evidence for any cofactors in the animal enzymes. Again in contrast to monoamine oxidase, diamine oxidase is inhibited by excess substrate. This is interpreted as showing combination of the enzyme with separate substrate molecules at the two adsorbing sites in this situation there is no effective reaction, as the catalysis appears to require combination of the substrate at two points. 

Cellular processes require orthogonal catalysts, that is, ones that can function unaffected by all the other cell components. Organometallic catalysts often fail to act in concert with enzymes because of mutual inactivation. A Cp Ir(chelate)Cl transfer hydrogenation catalyst has now been successfully incorporated into the protein, streptavidin, as an artificial transfer hydrogenase in order to protect it from deactivation in cooperative catalysis with monoamine oxidases. ... 

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