title: Hydrolysis of the four stereoisomers of soman catalyzed by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma.
abstract: 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.
authors.affiliation: Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
authors.forename: L P
authors.initials: LP
authors.lastname: de Jong
authors.forename: C
authors.initials: C
authors.lastname: van Dijk
authors.forename: H P
authors.initials: HP
authors.lastname: Benschop
mesh_terms: 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
chemical_list: D004798:Enzymes; D012999:Soman