Sparteine oxidation by the human liver: absence of inhibition by mephenytoin. 1984

M Jurima, and T Inaba, and W Kalow

Recent population data suggest independence of the genetic polymorphisms in mephenytoin and sparteine/debrisoquine oxidation. We used human liver preparations to test whether mephenytoin competes with sparteine for binding to the genetically variable cytochrome P-450, which mediates metabolism of both sparteine and debrisoquine. Mephenytoin failed to inhibit in vitro sparteine oxidation. This provides biochemical evidence that the polymorphism of sparteine/debrisoquine metabolism is not related to that of mephenytoin.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008617 Mephenytoin An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias. Methoin,Methyl Phenetoin,5-Ethyl-3-Methyl-5-Phenylhydantoin,Mefenetoin,Mesantoin,Phenantoin,5 Ethyl 3 Methyl 5 Phenylhydantoin,Phenetoin, Methyl
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
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006827 Hydantoins Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS. Hydantoin,Imidazolidine-2,4-Diones,Imidazolidine 2,4 Diones
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013034 Sparteine A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype. 7,14-Methano-2H,6H-dipyrido(1,2-a:1',2'-e)(1,5)diazocine, dodecahydro-, (7S-(7alpha,7aalpha,14alpha,14abeta))-,Lupinidin,Lupinidine,Pachycarpine,D-sparteine,Depasan Retard,Genisteine Alkaloid,L-Sparteine,Pachycarpine Sulfate (1:1), Pentahydrate, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydrochloride, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydrochloride, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Hydroiodide, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Monohydrochloride, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Monohydroiodide, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Sulfate,Sparteine Sulfate (1:1), (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer,Sparteine Sulfate (1:1), (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine Sulfate Anhydrous,Sparteine, (+)-Isomer,Sparteine, (-)-Isomer,Sparteine, (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine, (7R-(7alpha,7abeta,14alpha,14abeta))-Isomer,Sparteine, (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer,Sparteine, (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer,Sparteine, (7S-(7alpha,7abeta,14alpha,14abeta))-Isomer,alpha-Isosparteine,beta-Isosparteine,Anhydrous, Sparteine Sulfate,Sulfate Anhydrous, Sparteine,alpha Isosparteine,beta Isosparteine
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

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