Stereoselective hydrolysis of soman in human plasma and serum

Abstract

The contribution of various human serum and plasma fractions to the total hydrolysis rate constants of the four isomers of soman is studied. Spontaneous hydrolysis (as measured in buffer) occurs at a faster rate for the C(+)P(+)- and C(−)P(−)-isomers. A stereoselectively catalyzed hydrolyis of soman occurs in serum fractions IV and V (albumin). In fraction V the C(+)P(+)- and C(−)P(−)-isomers are hydrolyzed at a faster rate than their respective epimers, while in fraction IV-1 a stereoselective effect towards C(+)P(+)-soman is found. All the forementioned contributions, however, are negligible in comparison with the stereoselective enzymatic hydrolysis of the P(+)-isomers. The latter reaction is characterized by a significant lowering of the activation energy as compared with the spontaneous hydrolysis of the P(+)-isomers. Such a lowering in activation energy is not found for the hydrolysis of the P(−)-isomers in whole serum or plasma; hence it can be concluded that a phosphorylphosphatase hydrolyzes the P(+)-isomers in a stereoselective way, the P(−)-isomers either not being affected by this (these) enzyme(s) or the mechanism of catalysis being fundamentally different. This conclusion is in agreement with the observations on the influence of Hg 2+ on the hydrolysis of soman in serum; the hydrolysis of the P(+)-isomers is significantly inhibited by 1 mM of Hg 2+ while the P(−)-hydrolysis is unaffected by this concentration of Hg 2+. The action of some potential inhibitors on this phosphorylphosphatase activity was studied. Iodoacetate did not inhibit nor did Ba 2+ Sr 2+, Co 2+ or Mn 2+ show a significant effect on the hydrolysis of the P(+)-isomers. On the other hand the hydrolytic activity in serum was nearly completely inhibited by EDTA but restored upon addition of Ca 2+. These findings suggest that this enzymatic activity can be classified as an arylesterase (paraoxonase). Finally, the influence of pH on the hydrolytic activity shows a different pattern for C(+)P(+)- and C(−)P(+)soman, which may suggest that more than one enzyme is involved in the degradation of soman.