Phenol sulfate conjugation

At higher levels of phenols in the diet, glucuronic acid conjugation of phenols predominates over sulfate conjugation. This is attributed to the fact that the rate of glucuronic acid conjugation of phenols is proportional to the body levels of phenols. Sulfate conjugation, on the other hand, is independent of the phenol level and primarily depends upon the availability of sulfate in the body. Under normal circumstances, the byproducts of phenol metabolism are readily removed from the body by excretion via the kidneys. 

Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

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. 

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

The present paper deals with a relation between toxicity and accumulation of chlorophenols in goldfish, Carassius auratus, PCP metabolites and their amounts excreted by the three major routes (branchial, renal and biliary) in the fish, and also with effects of pre-exposure to PCP on PCP-tolerance and on sulfate conjugation with phenol by the liver soluble fraction of the fish. 

In our previous studies on the sulfate conjugation of phenols by fish livers, all the liver slices of the test fish and shellfish exhibited sulfate conjugation activities with phenol(14), and among various liver cell fractions separated by ultracentrifugation, only the soluble fraction displayed the sulfate conjugation activity for phenol and various phenolic compounds(15). 

Cytochrome P4502E1, also microsomally located, catalyzes the hydroxylation of phenol to form hydroquinone (and to a much lesser extent catechol), which is then acted upon by the phase II enzymes (Benet et al. 1995 Campbell et al. 1987 Gut et al. 1996 McFadden et al. 1996). All three enzyme systems are found in multiple tissues and there is competition among them not only for phenol but for subsequent oxidative products, like hydroquinone. As a consequence, the relative amount of the products formed can vary based on species, dose and route of administration. In vivo, the gastrointestinal tract, liver, lung, and kidney appear to be the major sites of phenol sulfate and glucuronide conjugation of simple phenols (Cassidy and Houston 1984 Powell et al. 1974 Quebbemann and Anders 1973 ... 

A number of enzymes known as sulfuric ester hydrolases (EC 3.1.6) are able to hydrolyze sulfuric acid esters. They comprise arylsulfatase (sulfatase, EC 3.1.6.1), steryl-sulfatase (steroid sulfatase, steryl-sulfate sulfohydrolase, arylsulfatase C, EC 3.1.6.2), choline-sulfatase (choline-sulfate sulfohydrolase, EC 3.1.6.6), and monomethyl-sulfatase (EC 3.1.6.16). Whereas mono-methyl-sulfatase is highly specific and does not act on higher homologues, arylsulfatase has a broad substrate specificity and is of particular significance in the hydrolysis of sulfate conjugates of phenols, be they endogenous compounds, drugs, or their metabolites [167-169],... 

Soluble cytoplasmic sulfotrans-ferases conjugate activated sulfate (3 -phosphoadenine-5 -phosphosulfate) with alcohols and phenols. The conjugates are acids, as in the case of glucuronides. In this respect, they differ from conjugates formed by acetyltransfe-rases from activated acetate (acetyl-coenzyme A) and an alcohol or a phenol... 

Sulfotransferases (SULTs) are important for the metabolism of a number of drugs, neurotransmitters, and hormones, especially the steroid hormones. The cosubstrate for these reactions is 3 -phosphoadenosine 5 -phosphosulfate (PAPS) (Fig. 4.1). Like the aforementioned enzymes, sulfate conjugation typically renders the compound inactive and more water soluble. However, this process can also result in the activation of certain compounds, such as the antihypertensive minoxidil and several of the steroid hormones. Seven SULT isoforms identified in humans, including SULTs lAl to 1A3, possess activity toward phenolic substrates such as dopamine, estradiol, and acetaminophen. SULTIBI possesses activity toward such endogenous substrates as dopamine and triiodothyronine. SULTIEI has substantial activity toward steroid hormones, especially estradiol and dehydroepiandrosterone, and toward the anti-... 

Benzbr anchracene /raw-3,4-dihydrodiol, bcnzf lanthracene /raw-8,9-dihydrodiol, benzfc anthracene /raw-10,11-dihydrodioI, phenolic and tetrahydroxy derivatives of benz[rf]anchracene, glucuronide and sulfate conjugates. 

The metabolism of thiophene (100) was first studied in 1886 by Heffter (1886MI10900), who administered it orally to dogs and noted the increased output of ethereal sulfates in urine. This is typical of aromatic hydrocarbons conversion to phenolic products which are excreted in urine as sulfate conjugates. When fed to rabbits, there was no increase in the ethereal sulfate output, but there was some indirect evidence of the presence in urine of dihydrodiols and thienylmercapturic acids (45MI10900). This was confirmed by Bray and coworkers (71MI10906,68BJ(109)11P>, who studied thiophene and benzothiophene metabolism in rabbits and rats. The only identifiable metabolites in urine were the thienylmercapturic acids (101) and (102), which are probably formed via conjugation of the intermediate... 

Studies on the metabolic fate of phenol in several species have indicated that four urinary products are excreted (Figure 9.5). Although extensive phenol metabolism takes place in most species, the relative proportions of each metabolite produced varies from species to species. In contrast to the cat, which selectively forms sulfate conjugates, the pig excretes phenol exclusively as the glucuronide. This defect in sulfate conjugation in the pig is restricted to only a few substrates, however, and may be due to the lack of a specific phenyl sulfotransferase because the formation of substantial amounts of the sulfate conjugate of 1-naphthol clearly indicates the occurrence of other forms of sulfotransferases. 

Sulfate conjugation Phosphoadenosyl phosphosulfate Sulfotransferase (cytosol) Phenols, alcohols, aromatic amines Estrone, aniline, phenol, 3-hydroxy-coumarin, acetaminophen, methyldopa... 

Although it has been stated that only phenols are conjugated with sulfuric acid,1 three urinary steroid sulfate esters (androsterone sulfate, dehydro-epi-androsterone sulfate, and A 6-aZZo-pregnene-3(/3)-ol-20-one sulfate) have been isolated in which the sulfuric acid is esterified by an alcoholic hydroxyl group.111 It is true that no alcohol administered to... 

It is assumed that phenols can conjugate directly with D-glucuronic acid or sulfuric acid. The scheme explains why phenols do not conjugate with mercapturic acid. Parke and Williams128 have recently shown that administration of phenylmercapturic acid or phenylcysteine to the rabbit is followed by the excretion of phenylcysteine, ester sulfates, and thio-phenol, and phenylcysteine also yields diphenyl disulfide. The thiol donor... 

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