Biomaterial Database

Stereoselective glucuronidation of zileuton isomers by human hepatic microsomes. 1995

D J Sweeny, and H N Nellans

Department of General Pharmacology, Abbott Laboratories, Abbott Park, IL 60064-3500.

The glucuronidation of the R-isomer and S-isomer of the 5-lipoxygenase inhibitor zileuton was examined using human hepatic microsomes. The glucuronidation of both isomers followed Michaelis-Menten kinetics, but glucuronidation rates were between 3.6- and 4.3-fold greater for the S-isomer. The apparent Km's (microM) for the R-isomer (392.9 +/- 35.9) and S-isomer (322.5 +/- 22.0) glucuronidation were similar, whereas the apparent Vmax (nmol/mg protein/min) was 3.4-fold greater for the S-isomer (5.2 +/- 0.7). In combination, each isomer competitively inhibited the glucuronidation of its antipode. The average Ki (microM) determined for S-isomer inhibition of R-isomer glucuronidation (197.8 +/- 61.3) was 2.4-fold lower than the Ki for the reciprocal interaction. These data indicate that the glucuronidation of the zileuton isomers in human hepatic microsomes is stereoselective. This stereoselective glucuronidation may be the basis for the more rapid clearance of the S-isomer observed in humans receiving zileuton.

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
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
D002877	Chromosomes, Human	Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.	Chromosome, Human,Human Chromosome,Human Chromosomes
D005965	Glucuronates	Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.	Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006918	Hydroxyurea	An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.	Hydroxycarbamid,Hydrea,Oncocarbide
D000894	Anti-Inflammatory Agents, Non-Steroidal	Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.	Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
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