Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the dog, the major excretory metabolite of the antidepressant sertraline was characterized as sertraline carbamoyl-O-glucuronide. The intact conjugate was isolated from bile by HPLC. The metabolite was labile to beta-glucuronidase and produced sertraline as the single hydrolytic product, based on HPLC and GC-MS analyses. By fast atom bombardment MS analysis, [M+H]+ and [M+Na]+ ions at m/z 526 and 548 were observed, as were the proton and sodium adducts of the aglycone (m/z 350 and 372) due to cleavage of the glycosidic bond and elimination of the glucuronic acid moiety (176 amu). The observed mass of the aglycone was 44 amu greater than sertraline, indicating that a carbamic acid of this secondary amine was conjugated with glucuronic acid. These data suggest that sertraline in solution reversibly associates with CO2 before formation of sertraline carbamoyl-O-glucuronide. This novel amine glucuronide was also identified in human plasma after the oral administration of sertraline to each of seven subjects. The glucuronide was stable in plasma at both acidic and basic pH.
 ...
PMID:Characterization of a carbamic acid ester glucuronide of the secondary amine sertraline. 256 71

A new glucuronylated prodrug of nornitrogen mustard, incorporating the same spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen mustard alone. This is explained by cyclization of the intermediate carbamic acid to the inactive chloroethyl oxazolidinone.
 ...
PMID:Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard. 1096 80

The absorption, metabolism, and excretion of N-[3-fluoro-4-[2-(propylamino)ethoxy]phenyl]-4,5,6,7-tetrahydro-4-oxo-1H-indole-3-carboxamide monomethanesulfonate (1), a GABAA receptor partial agonist potentially useful in treating generalized anxiety disorder, have been evaluated in both Sprague-Dawley rats and cynomolgus monkeys using [14C]1. In both species, mass balance was achieved within 48 h postdose, with the majority of drug-related material excreted within the feces; the clearance of 1 in each species had both metabolic and renal components. In addition to the metabolites produced by aliphatic hydroxylation and/or N-dealkylation of 1, two unique metabolites were detected: a putative carbamic acid (M7) in rat plasma and monkey bile, and an N-carbamoyl glucuronide (M8) in both rat and monkey bile. Metabolite M8 was structurally deciphered by liquid chromatographytandem mass spectrometry and NMR, and was readily generated in vitro upon incubation of [14C]1 with rat liver microsomes fortified with uridine 5'-diphosphoglucuronic acid trisodium salt and alamethicin under a CO2 atmosphere. Treatment of M8 with beta-glucuronidase afforded 1 directly. The presence of M8 in bile and its notable absence from other matrices suggests the enterohepatic cycling of 1 via M8. Although the structure of M7 was not elucidated unequivocally due to its inability to be formed in vitro and its minimal absolute quantities in limited biological matrices, data herein clearly support its structural rationalization. Furthermore, since M7 is the precursor of M8, detection of M8 is indirect evidence of its existence. It is proposed that M7 arises from an equilibrium between 1 and dissolved CO2-equivalents both in vivo and in vitro, similar to carbamino bonds observed in hemoglobin and certain amino acids, respectively.
 ...
PMID:Biotransformation of a GABAA receptor partial agonist in sprague-dawley rats and cynomolgus monkeys: identification of two unique N-carbamoyl metabolites. 1608 72