Biomaterial Database

S-oxidative cleavage of farnesylcysteine and farnesylcysteine methyl ester by the flavin-containing monooxygenase. 1994

S B Park, and W N Howald, and J R Cashman

Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.

Posttranslational modification of proteins with a farnesyl or geranylgeranyl group appears to be crucial in the signal transduction of eukaryotic cells. For example, farnesylation of ras-encoded proteins is a key process that apparently leads to membrane association of proteins that perform a function in cell growth-promoting activity. Although it has been suggested that prenylation of proteins may be an important regulatory mechanism, little is known about the mechanism whereby prenylated proteins are removed from the membrane. In our previous report [(1992) Chem. Res. Toxicol. 5, 193-201], we showed that S-alkenylated cysteines and mercapturates of xenobiotics were S-oxygenated by the flavin-containing monooxygenase. The S-oxides were not indefinitely stable and rearranged or underwent elimination reactions that cleaved the C-S(O) bond. As a model for farnesylated proteins and peptides, the biotransformation of farnesylcysteine methyl ester was examined in the presence of pig liver microsomes. Two prominent products were formed: farnesyl methyl ester sulfoxide and farnesylcysteine, arising from the action of the flavin-containing monooxygenase and esterase of pig liver, respectively. Formation of farnesylcysteine methyl ester sulfoxide by the flavin-containing monooxygenase was stereoselective (i.e., 71.5%:28.5%, major to minor diastereomer) in good agreement with previously reported stereoselectivity studies of other related S-alkylcysteine-containing compounds. That the stereoselectivity observed was due to S-oxygenation of the sulfur atom was verified in parallel chemical oxidation studies by using micellar electrokinetic capillary chromatography. Farnesylcysteine methyl ester was an excellent substrate for the flavin-containing monooxygenase, and the S-oxide product was confirmed by HPLC electrospray mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010105	Oxygenases	Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.	Oxygenase
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003545	Cysteine	A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.	Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013552	Swine	Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).	Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D017368	Protein Prenylation	A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.	Post-Translational Isoprenylation,Protein Isoprenylation,Protein Farnesylation,Protein Geranylgeranylation,Protein Polyisoprenylation,Farnesylation, Protein,Geranylgeranylation, Protein,Polyisoprenylation, Protein,Prenylation, Protein
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In