Farnesyl pyrophosphate synthetase. Mechanistic studies of the 1'-4 coupling reaction with 2-fluorogeranyl pyrophosphate.

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Publication Type Journal Article
School or College College of Pharmacy; College of Science; School of Medicine
Department Biochemistry; Medicinal Chemistry; Chemistry
Creator Poulter, Charles Dale
Other Author Argyle, J. Craig; Marsh, Eugene A.
Title Farnesyl pyrophosphate synthetase. Mechanistic studies of the 1'-4 coupling reaction with 2-fluorogeranyl pyrophosphate.
Date 1978-10-25
Description The mechanism of the 1'-4 coupling reaction between isopentenyl pyrophosphate and geranyl pyrophosphate catalyzed by farnesyl pyrophosphate synthetase from porcine liver was studied with the allylic substrate analogue 2-fluorogeranyl pyrophosphate. 2-Fluorogeranyl pyrophosphate is an alternate substrate for the enzyme, yielding 6-fluorofarnesyl pyrophosphate upon condensation with isopentenyl pyrophosphate. The Michaelis constant for the fluoroanalogue, Km = 1.1 micron, is similar to that measured for geranyl pyrophosphate, Km = 0.7 micron. However, the rate of condensation with the fluoroanalogue was only 8.4 X 10(-4) that of the normal reaction. A similar rate of depression (4.4 X 10(-3)) was found for solvolysis of geranyl methanesulfonate and the corresponding 2-fluoro derivative, reactions known to proceed via cationic intermediates. In contrast, displacement of chlorine from geranyl chloride and 2-fluorogeranyl chloride by cyanide showed a small (2-fold) rate enhancement for the fluoro compound. Finally, 2-fluorogeranyl pyrophosphate is a competitive inhibitor against geranyl pyrophosphate. These data are interpreted in terms of an ionization-condensation-elimination mechanism for the 1'-4 coupling reaction.
Type Text
Publisher American Society for Biochemistry and Molecular Biology (ASBMB)
Volume 253
Issue 20
First Page 7227
Last Page 7233
Subject Kinetics; Liver; Mass Spectrometry; Organophosphorus Compounds; Protein Binding
Subject MESH Dimethylallyltranstransferase; Terpenes; Transferases
Language eng
Bibliographic Citation J Biol Chem. 1978 Oct 25;253(20):7227-33. Poulter CD, Argyle JC, Mash EA. Farnesyl pyrophosphate synthetase. Mechanistic studies of the 1'-4 coupling reaction with 2-fluorogeranyl pyrophosphate. Retrieved April 16, 2007 from http://www.jbc.org/cgi/reprint/253/20/7227.
Rights Management Copyright © 1978 American Society for Microbiology. All rights reserved.
Format Medium application/pdf
Identifier ir-main,932
ARK ark:/87278/s66m3rd6
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 706847
Reference URL https://collections.lib.utah.edu/ark:/87278/s66m3rd6
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