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PHENYLALANINE 4-MONOOXYGENASE AND THE S-OXIDATION OF S-CARBOXYMETHYL-L-CYSTEINE IN HepG2 CELLS
| Content Provider | Scilit |
|---|---|
| Author | Boonyapiwat, Boontarika Panagopoulos, Panayotis Jones, Hevfin Mitchell, Stephen C. Forbes, Ben Steventon, Glyn B. |
| Copyright Year | 2005 |
| Abstract | The role of phenylalanine 4-monooxygenase (PAH) in the S-oxidation of S-carboxymethyl-L-cysteine (SCMC) in the rat has now been well established in rat cytosolic fractions in vitro. However, the role of PAH in the S-oxidation of SCMC in human cytosolic fractions or hepatocytes has yet to be investigated. The aim of this investigation was to analyse the kinetic parameters of PAH oxidation of both L-phenylalanine (Phe) and SCMC in the human HepG2 cell line in order to investigate the use of these cells as a model for the cellular regulation of SCMC S-oxidation. The experimentally determined Km and V(max) were 7.14 +/- 0.32 mM and 0.85 +/- 0.32 nmole Tyr formed min(-1) x mg protein(-1) using Phe as substrate. For SCMC the values were 25.24 +/- 5.91 mM and 0.79 +/- 0.09 nmole SCMC (RIS) S-oxides formed min(-1) x mg protein(-1). The experimentally determined Km and V(max) for the cofactor BH4 were 6.81 +/- 0.21 microM and 0.41 +/- 0.004 nmole Tyr formed min(-1) x mg protein(-1) for Phe and 7.24 +/- 0.19 microM and 0.42 +/- 0.002 nmole SCMC (R/S) S-oxides formed min(-1) x mg protein(-1) for SCMC. The use of various PAH inhibitors confirmed that HepG2 cells contained PAH and that the enzyme was capable of converting SCMC to its (R) and (S) S-oxide metabolites in an in vitro PAH assay. Thus HepG2 cells have become a useful additional tool for the investigation of the cellular regulation of PAH in the S-oxidation of SCMC. |
| Related Links | http://www.degruyter.com/downloadpdf/j/dmdi.2005.21.1/dmdi.2005.21.1.1/dmdi.2005.21.1.1.xml |
| ISSN | 07925077 |
| e-ISSN | 21910162 |
| DOI | 10.1515/dmdi.2005.21.1.1 |
| Journal | Drug metabolism and drug interactions |
| Issue Number | 1 |
| Volume Number | 21 |
| Language | English |
| Publisher | Walter de Gruyter GmbH |
| Publisher Date | 2005-01-01 |
| Access Restriction | Open |
| Subject Keyword | Drug Metabolism and Drug Interactions Protein Hepatocytes Pah Scmc Hepg2 Cells Vitro Experimentally Rat Carboxymethyl Journal: Drug metabolism and drug interactions, Vol- 21, Issue- 1 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology, Toxicology and Pharmaceutics Pharmacology (medical) |
