Mammals metabolic conjugation reactions

The mechanisms utilized by plants and mammals in the metabolism of xenoblotlcs are remeirkably similar. Similar classes of compounds or functional groups are frequently metabolized by comparable mechanisms. Oxidation, reduction, hydrolysis, and conjugation reactions occur with similar frequency in both. In most instances, however. 

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

The results of a comparative metabolism study of an aryl-sulfenyl derivative of carbofuran [2,2-dimethy1-2,3-dihydro-benzofuranyl-7 -methyl-N-(2-toluenesulfenyl)carbamate] in the house fly and white mouse Indicated the selective action of this compound to be a consequence of different metabolic pathways in insects and mammals (12). The arylsulfenyl group on the carbamate moiety allows the mammal to carry out metabolic reactions leading to less toxic products which are rapidly conjugated, while the toxic parent methylcarbamate is formed in the insect. 

In vivo intermediate in mammals by the detection of two of its derivatives,, the glutathione (GSH) conjugate and its further metabolites formed by an initial carbamylation reaction (W) (see below) and 2-chloroacrolein detected in the microsome-NADPH system and derived from the rearrangement-elimination reaction sequence discussed above (6). Sulfallate also yields 2-chloroacrolein in the microsome-NADPH system, presumably by -CH2 hydroxylation (22) on analogy with the metabolism of EPTC shown previously. 

In mammals, GSH S-conjugates, the metabolites of GSH S-transferase catalyzed reactions, are subject to further metabolism by a series of three enzyme-catalyzed reactions to form the corresponding N-acetylcysteine derivative or mercapturic acid, which is excreted in urine (3). The same group of three enzymes are also involved in recycling of GSH and in amino acid transport. The first step is catalyzed by y-glutamyltransferase (EC 2.3.2.2), an enzyme localized on the outer surface of most cells. This enzyme has been detected in A. suum (57), S. mansoni (58) and T. cruzi epimastigotes (59). However, there is no evidence that parasites metabolize GSH... 

---