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The mercapturic acid pathway.
Crit Rev Toxicol
November 2019
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA.
The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (-acetyl-l-cysteine -conjugates) are formed by the sequential action of the glutathione transferases, γ-glutamyltransferases, dipeptidases, and cysteine -conjugate -acetyltransferase to yield glutathione -conjugates, l-cysteinylglycine -conjugates, l-cysteine -conjugates, and mercapturic acids; these metabolites constitute a "mercapturomic" profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine -conjugates.
View Article and Find Full Text PDFA Complete Study of Farrerol Metabolites Produced in Vivo and in Vitro.
Molecules
September 2019
Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
Although farrerol, a characteristically bioactive constituent of L., exhibits extensive biological and pharmacological activities (e.g.
View Article and Find Full Text PDFIn vivo metabolic profiles of Bu-Zhong-Yi-Qi-Tang, a famous traditional Chinese medicine prescription, in rats by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.
J Pharm Biomed Anal
July 2019
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:
Bu-Zhong-Yi-Qi-Tang (BZYQT), a famous traditional Chinese medicine prescription (TCMP), has been extensively used for conditioning sub-health status and diseases caused by spleen-qi deficiency in China for over 700 years. BZYQT is prevalent not only in China, but also in Japan and South Korea for the clinical treatment of chronic diseases, such as fatigue, tuberculosis and loss of appetite after surgery. However, due to a lack of research on the holistic metabolism of BZYQT, the in vivo bioactive components of BZYQT remain unclear, hindering further study of its in vivo mechanism of action and quality control.
View Article and Find Full Text PDFγ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity.
Sci Rep
January 2019
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Article Synopsis
- GPNA is used mainly to block the glutamine transporter ASCT2, but it also affects other transporters and is broken down by the enzyme GGT.
- GGT catalyzes the breakdown of GPNA in lung cancer cells, leading to the release of toxic p-nitroaniline (PNA), which harms cell viability rather than simply inhibiting glutamine uptake.
- The study suggests that GPNA's role is more complicated than previously thought, indicating that new methods, like genetic suppression of ASCT2 or finding more specific inhibitors, may be needed for effective ASCT2 inhibition.
Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
Xenobiotica
August 2019
a Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry , Gdańsk University of Technology, Gdańsk , Poland.
Here, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxy-acridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined.
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