Trdan Lusin, Tina published the artcileEvaluation of bisphenol A glucuronidation according to UGT1A1*28 polymorphism by a new LC-MS/MS assay, Name: (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, the publication is Toxicology (2012), 292(1), 33-41, database is CAplus and MEDLINE.
The endocrine disruptor bisphenol A (BPA) is a frequently used chem. in the manufacture of consumer products. In humans, BPA is extensively metabolized to BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms. The study has been performed with the intention to improve the accuracy of published physiol. based pharmacokinetic models and to improve regulatory risk assessments of BPA. In order to gain insight into intestine, kidney, liver, and lung glucuronidation of BPA, human microsomes of all tested organs were used. BPAG formation followed Michaelis-Menten kinetics in the intestine and kidney, but followed substrate inhibition kinetics in the liver. Human lung microsomes did not show glucuronidation activity towards BPA. While the liver intrinsic clearance was very high (857 mL min-1 kg body weight-1), the tissue intrinsic clearances for the kidney and intestine were less than 1% of liver intrinsic clearance. Since BPA is a UGT1A1 substrate, we postulated that the common UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min-1 kg body weight-1, resp. Prior to microsomal experiments, the bioprodn. of BPAG and stable isotope-labeled BPAG (BPAGd16) was performed for the purpose of the reliable and accurate quantification of BPAG. In addition, a sensitive LC-MS/MS anal. method for the simultaneous determination of BPA and BPAG based on 2 stable isotope-labeled internal standards was developed and validated. In conclusion, our in vitro results show that the liver is the main site of BPA glucuronidation (K m 8.9 μM, V max 8.5 nmol min-1 mg-1) and BPA metabolism may be significantly influenced by a person’s genotype (K m 10.0-13.1 μM, V max 3.4-16.2 nmol min-1 mg-1). This discovery may be an important fact for the currently on-going worldwide BPA risk assessments and for the improvement of physiol. based pharmacokinetic models.
Toxicology published new progress about 267244-08-6. 267244-08-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Chiral,Carboxylic acid,Benzene,Phenol,Alcohol,Ether,, name is (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, and the molecular formula is C12H17NO2, Name: (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics