PMID: 701246Oct 25, 1978Paper

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

The Journal of Biological Chemistry
C D PoulterE A Mash

Abstract

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.

Citations

Sep 1, 2012·Biochemistry·Qi QianMartin E Tanner
Nov 4, 2011·Journal of the American Chemical Society·Nicole A Heaps, C Dale Poulter
Dec 12, 2012·Journal of the American Chemical Society·Juan A FaraldosRudolf K Allemann
Feb 25, 2011·The Journal of Organic Chemistry·Nicole A Heaps, C Dale Poulter
Mar 28, 2009·The Journal of Organic Chemistry·C Dale Poulter
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·David C HyattChulHee Kang
Sep 8, 2016·Biochemistry·Nuno M F S A CerqueiraP A Fernandes
Mar 14, 2008·Chembiochem : a European Journal of Chemical Biology·Lars BräuerLudger Wessjohann

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