Phenols conjugation with glucuronic acid

The nutritional value of the diet influences the ability of herbivores to detoxify plant secondary metabolites (Schwass and Finley, 1985). For instance, voles in winter have to consume the bark of birch Betula sp.). This causes stress and leads to poor growth and high mortality among young animals. Birch bark contains phenolics and terpenoids. Both are metabolized by cytochrome P450 monooxidases in phase I and conjugated with glucuronic acid in phase II. 

They provide examples of drugs which undergo sulphoxidation to yield sulphoxides and sulphones. In addition, A-oxidation (at the A °-position), hydroxylation of one or both of the aromatic rings, A-dealkylation of the A°-side-chain, and fission of the A°-side-chain may also occur. The phenolic metabolites are then conjugated with glucuronic acid or sulphate the metabolites are excreted in both the urine and the bile. 

Disposition in the Body. Absorbed after oral administration but undergoes extensive metabolism by demethylation, sulphoxida-tion, A-oxidation and aromatic hydroxylation, followed by conjugation with glucuronic acid. About 15 to 30% of an oral dose is excreted in the urine mainly as conjugated phenolic metabolites. 

Hydroxylation of one or both aromatic rings Conjugation of phenolic metabolites with glucuronic acid or sulfate Scission of the N10 side-chain... 

Hydroxylation of one aromatic ring Conjugation of phenolic products with glucuronic acid or sulfate Hydrolytic scission of the hydantoin ring at the bond between carbons-3 and -4 to give 5,5-diphenylhydantoic acid... 

N-deacylation of p-chlorobenzoyl group Both O-dealkylation and N-deacylation Conjugation of phenolic products with glucuronic acid Other conjugation products... 

N-dealkylation at N1 Hydroxylation at carbon-3 Conjugation of phenolic products with glucuronic acid Both N-dealkylation of N1 and hydroxylation at carbon-3... 

In the liver two phases of biotransformation reactions can take place phase I transformations that introduce polar groups (hydroxyls) in the molecule, and phase II reactions which include conjugations with glucuronic acid, sulphate, or glycine to yield water-soluble metabolites which are excreted in urine. 0-Methylations, to inactivate catechol moieties in these molecules, are also phase II reactions. Phase I reactions are not important in natural phenolic metabolites since they generally contain several polar hydroxyl groups). Phase II reactions increase the molecular weight of the phenolics and promote their secretion into bile. 

Dogs excrete p-hydroxybenzaldehyde (XLVI) as p-glucuronosidobenzoyl glucuronoside, p-hydroxyhippuric acid and possibly free p-hydroxybenzoic acid (67, 351). In the case of rabbits, however, p-glucuronosidobenzalde-hyde has been isolated from the urine as the 2,4-dinitrophenylhydrazone and it appeared probable that conjugation of the phenolic hydroxyl with glucuronic acid preceded oxidation of the aldehyde group (147). 

Analysis of the urine specimens of a 3-year-old boy who had been playing with 1,4-dichlorobenzene yielded 2,5-dichlorophenol as well as 4 other unidentified phenols. These compounds were shown to be conjugated with glucuronic and sulfuric acids (Hallowell 1959). 

Table 5.12 Conjugation of Phenol with Glucuronic Acid and Sulfate...

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 sulfate is zero in the pig but the facility is present in many other species. There are many... 

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