Glucuronidation of racemic O-desmethyltramadol, the active metabolite of tramadol.

O-Desmethyltramadol, the active metabolite of analgesic tramadol, is metabolised through glucuronidation. The present study was conducted to identify the human UDP-glucuronosyltransferases (UGTs) that catalyse the glucuronidation of O-desmethyltramadol, a racemic mixture of 1R,2R- and 1S,2S-enantiomers. We developed a fast and selective liquid chromatography-mass spectrometry method to separate, analyse and quantify the diastereomeric phenolic O-glucuronides of O-desmethyltramadol.

UDP-glucuronosyltransferases in conjugation of 5alpha- and 5beta-androstane steroids.

We have examined the glucuronidation of androsterone (5alpha-androstane-3alpha-ol-17-one), etiocholanolone (5beta-androstane-3alpha-ol-17-one), 5alpha-androstane-3alpha-,17beta-diol (5alpha-diol), and 5beta-androstane-3alpha-, 17beta-diol (5beta-diol) by 19 recombinant human UDP-glucuronosyltransferases (UGTs). The results reveal large differences in stereo- and regioselectivity between UGT2B7, UGT2B15, and UGT2B17. UGT2B7 conjugated all four androgens at the 3-OH but not at the 17-OH that is available in both diols.

Non-steroidal anti-inflammatory drugs interact with testosterone glucuronidation.

Testosterone and epitestosterone are secreted mainly as glucuronide metabolites and the urinary ratio of testosterone glucuronide to epitestosterone glucuronide, often called T/E, serves as a marker for possible anabolic steroids abuse by athletes. UDP-glucuronosyltransferase (UGT) 2B17 is the most important catalyst of testosterone glucuronidation. The T/E might be affected by drugs that interact with UGT2B17, or other enzymes that contribute to testosterone glucuronidation.

UDP-glucuronosyltransferases (UGTs) 2B7 and UGT2B17 display converse specificity in testosterone and epitestosterone glucuronidation, whereas UGT2A1 conjugates both androgens similarly.

Testosterone and epitestosterone are endogenous steroids that differ in the configuration of the hydroxyl-bearing carbon at C-17. Testosterone is the predominant male sex hormone, whereas the role of epitestosterone is largely unclear. In humans, both androgens are excreted mainly as glucuronide conjugates and the urinary ratio of testosterone to epitestosterone (T/E), used to expose illicit testosterone abuse by male athletes, indicates the relative concentrations of the respective glucuronides.

Prominent but reverse stereoselectivity in propranolol glucuronidation by human UDP-glucuronosyltransferases 1A9 and 1A10.

Propranolol is a nonselective beta-adrenergic blocker used as a racemic mixture in the treatment of hypertension, cardiac arrhythmias, and angina pectoris. For study of the stereoselective glucuronidation of this drug, the two propranolol glucuronide diastereomers were biosynthesized, purified, and characterized. A screen of 15 recombinant human UDP-glucuronosyltransferases (UGTs) indicated that only a few isoforms catalyze propranolol glucuronidation.