Glucuronidation, occurrence

Asai, A. and Miyazawa, T., Occurrence of administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma, Life Sci., 67, 2785, 2000. 

Zidovudine was the first drug of the class. It is a dideoxythymidine analog. It has to be phos-phorylated to the active triphosphate. This triphosphate is a competitive inhibitor of HIV reverse transcriptase. By incorporation into viral DNA it also acts as a chain-terminator of DNA synthesis. Mutations in viral reverse transcriptase are responsible for rapidly occurring resistance. Zidovudine slows disease progression and the occurrence of complications in AIDS patients. It is readily absorbed. However, first pass metabolism reduces its oral bioavailability with some 40%. It readily crosses the blood-brain barrier. Plasma protein binding is about 30%. Zidovudine is glucuronidated in the liver to an inactive metabolite. Its elimination half-life is 1 hour. 

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. 

Neutral loss Neutral loss monitoring allows the detection of any compound that loses a specified mass during CID. This scan type allowed to detect any glucuronides (neutral loss of 176 Da), sulpho-conjugates (loss of 80 Da) and was helpful to identify molecules that lose a tropic acid moiety (loss of 166 Da) or a tropic acid-derived HCOH group (loss of 30 Da) [51, 52], The occurrence of the latter losses provided helpful hints for the presence of an (partly) unaltered tropic acid moiety in, e.g. atropine. 

Harborne and Saleh (1971) confirmed the presence of quercetin 3-arabinoside in the leaves of fennel and three other flavo-nol glycosides, kaempferol 3-arabinoside, kaempferol 3-glucuronide and quercetin 3-glucuronide. A chemotypic characterization of populations of fennel based on the occurrence of glycosides has been attempted. The dried distillation residue of fennel fruits contains 14-22% protein and 12-18% fat and is suitable for stock feed (Weiss, 2002). 

Biosynthetic considerations and the discovery of their co-occurrence with a-cedrene (42) and (+)-zizaene (43) have led to the reformulation of various cedrane derivatives (44 R = Me, CH2OH, CHO, or COzH) found in vetiver oil 76 it is believed that these sesquiterpenoids are formed from the common precursor (45). The metabolites of cedrol found in the urine of rabbits are mainly glucuronides of hydroxylated cedrol derivatives 77 presumably formation of the glucuronide of the tertiary alcohol itself is difficult because of steric hindrance. 

Bile alcohols are polyhydroxy C27 sterols that serve as intermediates in the biosjmthesis of cholic acid and chenodeoxycholic acid from cholesterol (1, 2). Recently several studies have shown that increased amounts of bile alcohols namely 27-nor-5p-cholestane-3a,7a,12a,24, 25-pentol and 5P-cholestane-3a, 7a,12a,25,26-pentol are excreted (as glucuronides in urine of patients with liver diseases such as primary biliary cirrhosis (3), liver cirrhosis (4, 5) and a-antitrypsin deficiency (6). Ichimiya et. al., described the occurrence of 5P-cholestane-3a,7a,12a,26,27-pentol (5P-cyprinol) and 5P-cholestane-3a,7a,... 

In veterinary medicine, boldenone, a synthetic anabolic steroid (Figure 2.1), is commercially available, hence it is a concern in the horseracing industry. Pu et al. (2004) used ion-trap LC-MS analysis to detect boldenone conjugates (sulfate and glucuronide) and their 17-epimers in horse mine after intramuscular administration of boldenone undecylenate. Soon afterwards. Ho et al. (2004) reported the occurrence of endogenous boldenone sulfate in the urine of uncastrated male horses, and quantitated it by quadrupole time-of-flight (Q-TOF) LC-MS-MS. 

Belfroid AC, Van der Horst A, Vethaak AD, Schafer AJ, Rijs GBJ, Wegener J, Cofino WP (1999) Analysis and occurrence of estrogenic hormones and glucuronides in surface water and wastewater in The Netherlands. Sci Total Environ 225, 101-108. 

---