PMID: 7011364Feb 3, 1981Paper

Irreversible inhibition of glutamate decarboxylase by alpha-(fluoromethyl)glutamic acid

Biochemistry
D Kuo, R R Rando

Abstract

alpha-(Fluoromethyl)glutamic acid (FMG) was synthesized and shown to be an active site directed irreversible inhibitor of glutamate decarboxylase (EC 4.1.1.15) from Escherichia coli. The KI for the active enantiomer is 1.4 microM, and the kinh = 5.9 X 10(-3) s-1. Substrates for the enzyme, such as L-glutamate, and competitive inhibitors, such as citrate, decrease the rates of FMG-mediated inactivation of the enzyme. A profound change in the ultraviolet spectrum of the enzyme accompanies the inactivation process. When [3H]-FMG is used, it can be shown that the enzyme incorporates radioactivity at the same rate as that of inactivation. There is a 1:1 stoichiometry of [3H]FMG incorporated to pyridoxal phosphate binding subunits of the enzyme. From these and other studies it is concluded that FMG is a substrate for the enzyme and alkylates it as a consequence of this turnover.

Citations

Jul 1, 1983·Archives of Microbiology·K PrabhakaranW F Kirchheimer
Feb 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·G K Surya PrakashGeorge A Olah
Feb 15, 1983·Biochemical Pharmacology·A J CooperP Dowd

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biosynthetic Transformations

Biosyntheic transformtions are multi-step, enzyme-catalyzed processes where substrates are converted into more complex products in living organisms. Simple compounds are modified, converted into other compounds, or joined together to form macromolecules. Discover the latest research on biosynthetic transformations here.