Mammals glutathione conjugate

Figure 3. Glutathione conjugation of naphthalene in mammals is a classic example of in vivo conjugate formation (Nap-GSH) that is not evident by the nature of metabolites (mercapturlc acids) recovered from the urine.

The common terminal metabolite of a glutathione conjugate In a mammal Is a mercapturlc acid —-an N-acetyl- -substltuted-L-cystelne. The equivalent In the plant the phytomercapturlc acid — Is an N-malonyl- -substltuted-L-cystelne (Figure 3). The susceptibility of the -malonyl group to hydrolysis In the mammal has not, to our knowledge, been studied. If It Is stable then the phytomercapturlc acid Is likely to be eliminated unchanged (or perhaps S oxldlzed). 

Ester hydrolysis is the most important microbial degradation of diazinon, whereas mammals produce glutathione conjugates and oxidation products. 

Mercapturic acid formation has been shown to occur in a variety of mammals, birds, reptiles, amphibians and fish. Insects also form glutathione conjugates but do not N-acylate the eventual S-substituted cysteine derivatives to any great extent. It is also possible that the S-carboxyalkylcysteines of plants have a similar genesis. Mercapturic acid formation is certainly one of the best studied and documented protective functions for glutathione. 

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. 

Excretion of the electrophilic intermediates as conjugated derivatives has been well identified in terrestial mammals as well as in marine species. All marine species investigated are able to conjugate the oxide intermediates to GSH-derivatives (Bend etaL, 1977). Generally, invertebrates show lower activity than vertebrates. In addition, wide variation in glutathione-S-transferase activity has been observed beween species and substrates used. Reasonable experimental evidence now exists for the enzyme-mediated biotransformation of petroleum hydrocarbons in several marine fish and invertebrate species. 

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