Hydrolysis of the four stereoisomers of soman catalyzed by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma.
Stereoselective hydrolysis at pH 7.5 and 37 degrees of C(+/-)P(+/-)-soman by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma is studied by using the four single stereoisomers. The fast hydrolysis of the C(+/-)P(+)-isomers is monitored titrimetrically, whereas the decay of the much slower reacting C(+/-)P(-)-isomers is followed by gas chromatographic determination of the residual concentration. Values of Km and Vmax are evaluated for the enzymatic hydrolysis of the two relatively nontoxic C(+/-)P(+)-isomers. The plasma enzymes have a high affinity for these isomers (Km: 0.01-0.04 mM); the Km values of the liver enzymes vary between 0.04 and 0.7 mM. Except for rat liver homogenate, only first-order rate constants can be obtained for catalyzed hydrolysis (kc) of the highly toxic C(+/-)P(-)-isomers: most measurements with C(+/-)P(-)-isomer concentrations greater than 0.3 mM are complicated by epimerization to C(+/-)P(+)-isomers, which may conceal enzyme saturation with the C(+/-)P(-)-isomers. The first-order rate constants of catalyzed hydrolysis (Vmax/Km or kc) by all liver homogenates and plasmata decrease in the order: C(+)P(+)- greater than C(-)P(+)- much greater than C(-)P(-)- greater than C(+)P(-)-soman. The highest P(+)-/P(-)-stereoselectivity is found for rat plasma. Rat liver homogenate is more potent than the other liver homogenates in catalyzing the hydrolysis of both the C(+/-)P(+)- and the C(+/-)P(-)-isomers. Rat plasma shows the highest activity for degradation of the C(+/-)P(+)-isomers, but is approximately as active as marmoset and human plasma for degradation of the C(+/-)P(-)-isomers.
de Jong
L P
LP
Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
van Dijk
C
C
Benschop
H P
HP
D000818:Animals; D001769:Blood / Q000378:metabolism*; D002144:Callithrix; D002849:Chromatography, Gas; D004798:Enzymes / Q000097:blood / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051381:Rats; D012999:Soman / Q000032:analysis / Q000378:metabolism*; D013237:Stereoisomerism
D004798:Enzymes; D012999:Soman