Glucuronic acid conjugates species differences

Although UGTs catalyze only glucuronic acid conjugation, CYPs catalyze a variety of oxidative reactions. Oxidative biotransformations include aromatic and side chain hydroxylation, N-, O-, S-dealkylation, N-oxidation, sulfoxidation, N-hydroxylation, deamination, dehalogenation and desulfation. The majority of these reactions require the formation of radical species this is usually the rate-determining step for the reactivity process [28]. Hence, reactivity contributions are computed for CYPs, but a different computation is performed with the UGT enzyme (as described in Section 12.4.2). 

Absorption of pentachlorophenol is relatively rapid in all species studied, but elimination differs between species and also between sexes. Metabolism occurs through glucuronic acid conjugation and hydrolytic dechlorination to tetrachlorohydroquinone, which is further conjugated. In contrast to rodents, rhesus monkeys eliminate pentachlorophenol in urine unchanged (lARC, 1991). 

Reduced testes weights and histologic evidence of testicular injury were found in rats and guinea pigs but not hamsters or mice fed 2g/l /day DBP for 10 days, indicating a species-specific response. The basis of this species variation may be related to species differences in the ability to conjugate monobutyl phthalate, the primary metabolite of DBP, with glucuronic acid. ... 

The conjugation of phenol with glucuronic acid is zero in the cat but the facility is present in many other species. Conversely, the conjugation of phenol with sulphate is zero in the pig but the facility is present in many other species. There are many quantitative (and qualitative) differences in the conjugation of arylacetic acids with amino acids. 

On the basis of kinetic studies [75-77], Smith suggested that the major factors governing the choice of two alternative metabohc routes are the first-and zero-order rate constants of the two reactions. The first-order rate constant in conjugation reactions may not be subject to serious species variations, but the zero-order rate constant depends not only on the mobihzation rate of glycine, glucuronic acid, etc., which is different in different species, but also on the compound metabohzed. The compound may affect the zero-order rate constant either by virtue of its tissue level, which depends on dose, or by its effect on the maximum velocity of the enzymatic reaction [23]. 

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