Hydrolysis species differences

NADPH-independent hydrolytic metabolism. The CLint for deltamethrin was estimated to be twice as rapid in humans as in rats on a per kg body weight basis. Metabolism by purified rat and human CESs was used to examine further the species differences in hydrolysis of deltamethrin and esfenvalerate. Results of CES metabolism revealed that hCEl was markedly more active toward deltamethrin than the Class I rat CESs, hydrolase A and B, and the Class II human CES, hCE2 however, hydrolase A metabolized esfenvalerate twice as fast as hCEl, whereas hydrolase B and hCEl hydrolyzed esfenvalerate at equal rates. These studies demonstrated a significant species difference in the in vitro pathways of biotransformation of deltamethrin in rat and human liver microsomes, which was due in part to differences in the intrinsic activities of rat and human CESs. 

Marked species differences in hydrolytic cleavage were also observed for pranlukast (4.160), a leukotriene receptor antagonist. In rats, amide hydrolysis represented a major metabolic pathway, whereas, in humans, it was apparently absent. Investigations with purified enzymes showed that pranlukast... 

Y. Yoshigae, T. Imai, A. Horita, M. Otagiri, Species Differences for Stereoselective Hydrolysis of Propranolol Prodrugs in Plasma and Liver , Chirality 1997, 9, 661 -666. 

Interestingly, there is a marked species difference in the in vitro hydrolysis of carbamazepine 10,11-epoxide, such that the reaction was observed only in liver microsomes from humans but not in liver microsomal or cytosolic preparations from dogs, rabbits, hamsters, rats, or mice [181][196], Thus, carbamazepine appears to be a very poor substrate for EH, in analogy with the simpler analogues 10.129 (X = RN, RCH, or RCH=C). The human enzyme is exceptional in this respect, but not, however, in the steric course of the reaction. The diol formed (10.131, X = H2NCON) is mostly the trans-(10.S, 11. S )-enaniiomer [196], In other words, the product enantioselectivity of the hydration of carbamazepine epoxide catalyzed by human EH is the same as that of di benzol a,oxide catalyzed by rabbit microsomal EH, discussed above. 

The aquo-Fe " ion, [Fe(OH2)6], is the predominant Fe " species only at very low pH. As the pH rises above 1, Fe " hydrolyses in a stepwise manner to give a series of soluble, positive and (in alkaline media) negative hydroxo species (see Chap. 13). The different hydrolysis species raise the concentration of dissolved iron in equilibrium with the solid at any pH. The equilibrium between the solid oxide and its various hydroxo species in solution is represented by the equation ... 

Recall in our discussion of routes of biotransformation we considered species differences using malathion as an example. Insects convert this compound to its toxic oxidation product more quickly than they detoxify it by hydrolysis. Humans do the conversions in the opposite priority. However, the insects which might be different from the general population and perform detoxification reactions at a faster rate would survive pesticide application and their "resistant" genes would be selectively passed on to the next generations. 

Kedderis, GL. Batra, R. (1993) Species differences in the hydrolysis of 2-cy anoethylene oxide, the epoxide metabolite of acrylonitrile. Carcinogenesis, 14, 685-689... 

Comparative Toxicokinetics. The toxicity of DEHP differs among species. This is due both to differences in pharmacokinetics and species-specific differences in target tissue susceptibilities. For example, there are species differences in the rate of hydrolysis of DEHP to MEHP in the intestine. Hydrolytic activity is highest in the mouse, followed by the rat, guinea pig and hamster (Albro 1986 ... 

A plot of p([Cu2 ]/[Cu7ot]) 3S a function of pH for three separate titrations fall on a single curve despite up to fivefold differences in measured dissolved copper concentration at a given pH (Figure 2). This behavior of the ratio [Cu2+]/[Cujot] is indicative of the formation of mononuclear hydrolysis species and excludes the possibility that the observed reduction in free cupric ion may have been caused by precipitation of Cu(0H)2 (solid) or the formation of polynuclear complexes. Analysis of data for p[Cu2+], pECujoj] and pH in the pH range 7.7 to 10.8 indicated the presence of two hydrolysis species (CuOH and Cu(0H)2) whose stability constants are given in Table I. Our value of the stability constant for the monohydroxo complex (106.48) falls... 

Their general conclusion was that, although various species differed quantitatively in the relative amounts of particular end products of atropine metabolism, the chemical changes undergone by the molecule In the various species were the same hydrolysis of the ester linkage, hydroxylatlon of the benzene nucleus, glucuronldatlon, and oxidation to C02 ... 

In most models involving multiple surface species these species differ in the number of protons released per one specifically adsorbed cation (or molecule of weak acid). As discussed in Section II, such models have firm physical grounds, namely they can be interpreted in terms of stepwise deprotonation of adsorbed molecules of multivalent acids (or hydrolysis of adsorbed heavy metal cations) as the pH increases. 

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