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Characterization and modulation by drugs of sheep liver microsomal flavin monooxygenase activity.
Cell Biochem Funct. 2005 Jul-Aug; 23(4):245-51.CB

Abstract

The flavin monooxygenases (FMO) catalyse the NADPH and oxygen-dependent oxidation of a wide range of nucleophilic nitrogen-, sulfur-, phosphorus-, and selenium heteroatom-containing chemicals, drugs, and agricultural agents. In the present study, sheep liver microsomal FMO activity was determined by measuring the S-oxidation rate of methimazole and the average specific activity obtained from different microsomal preparations was found to be 3.8 +/- 1.5 nmol methimazole oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 7). The presence of 0.1% Triton X-100 in the reaction mixture caused an increase of specific sheep liver microsomal FMO activity towards methimazole to 6.1 +/- 1.4 nmol methimazole oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 6). Metabolism of imipramine and chlorpromazine was measured by following the oxidation of cofactor NADPH spectrophotometrically at 340 nm. Sheep liver microsomal FMO activity towards imipramine and chlorpromazine was found to be 10.7 and 12.3 nmol NADPH oxidized min(-1) mg(-1) microsomal protein, respectively. Characterization of sheep liver enzyme was carried out using methimazole as substrate and the maximum FMO enzyme activity was detected at 37 degrees C and at pH 8.0. The apparent K(m) value of sheep liver microsomal FMO for methimazole was 0.118 mM. Effects of the detergents Triton X-100, Cholate, and Emulgen 913, on FMO activity were determined and FMO activity was found to increase with the addition of detergents to the reaction medium. Sheep liver microsomal FMO-catalysed methimazole oxidation was inhibited by imipramine and chlorpromazine when these drugs were used at high concentrations. Western blot-immunochemical analysis revealed the presence of FMO3 in sheep liver microsomes.

Authors+Show Affiliations

Can Demirdöğen B
Department of Biological Sciences, Middle East Technical University, Joint Graduate Program in Biochemistry, Ankara, Turkey.
Adali O
No affiliation info available

MeSH

AnimalsAntidepressive Agents, TricyclicAntipsychotic AgentsAntithyroid AgentsChlorpromazineCholatesDetergentsImipramineLiverMethimazoleMicrosomes, LiverNADPOctoxynolOxidation-ReductionOxygenasesSheep

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15473006

Citation

Can Demirdöğen, Birsen, and Orhan Adali. "Characterization and Modulation By Drugs of Sheep Liver Microsomal Flavin Monooxygenase Activity." Cell Biochemistry and Function, vol. 23, no. 4, 2005, pp. 245-51.
Can Demirdöğen B, Adali O. Characterization and modulation by drugs of sheep liver microsomal flavin monooxygenase activity. Cell Biochem Funct. 2005;23(4):245-51.
Can Demirdöğen, B., & Adali, O. (2005). Characterization and modulation by drugs of sheep liver microsomal flavin monooxygenase activity. Cell Biochemistry and Function, 23(4), 245-51.
Can Demirdöğen B, Adali O. Characterization and Modulation By Drugs of Sheep Liver Microsomal Flavin Monooxygenase Activity. Cell Biochem Funct. 2005 Jul-Aug;23(4):245-51. PubMed PMID: 15473006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization and modulation by drugs of sheep liver microsomal flavin monooxygenase activity. AU - Can Demirdöğen,Birsen, AU - Adali,Orhan, PY - 2004/10/9/pubmed PY - 2005/9/16/medline PY - 2004/10/9/entrez SP - 245 EP - 51 JF - Cell biochemistry and function JO - Cell Biochem Funct VL - 23 IS - 4 N2 - The flavin monooxygenases (FMO) catalyse the NADPH and oxygen-dependent oxidation of a wide range of nucleophilic nitrogen-, sulfur-, phosphorus-, and selenium heteroatom-containing chemicals, drugs, and agricultural agents. In the present study, sheep liver microsomal FMO activity was determined by measuring the S-oxidation rate of methimazole and the average specific activity obtained from different microsomal preparations was found to be 3.8 +/- 1.5 nmol methimazole oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 7). The presence of 0.1% Triton X-100 in the reaction mixture caused an increase of specific sheep liver microsomal FMO activity towards methimazole to 6.1 +/- 1.4 nmol methimazole oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 6). Metabolism of imipramine and chlorpromazine was measured by following the oxidation of cofactor NADPH spectrophotometrically at 340 nm. Sheep liver microsomal FMO activity towards imipramine and chlorpromazine was found to be 10.7 and 12.3 nmol NADPH oxidized min(-1) mg(-1) microsomal protein, respectively. Characterization of sheep liver enzyme was carried out using methimazole as substrate and the maximum FMO enzyme activity was detected at 37 degrees C and at pH 8.0. The apparent K(m) value of sheep liver microsomal FMO for methimazole was 0.118 mM. Effects of the detergents Triton X-100, Cholate, and Emulgen 913, on FMO activity were determined and FMO activity was found to increase with the addition of detergents to the reaction medium. Sheep liver microsomal FMO-catalysed methimazole oxidation was inhibited by imipramine and chlorpromazine when these drugs were used at high concentrations. Western blot-immunochemical analysis revealed the presence of FMO3 in sheep liver microsomes. SN - 0263-6484 UR - https://www.unboundmedicine.com/medline/citation/15473006/Characterization_and_modulation_by_drugs_of_sheep_liver_microsomal_flavin_monooxygenase_activity_ DB - PRIME DP - Unbound Medicine ER -