Drug metabolism, microsomal

Lipid-soluble xenobiotics are commonly biotra ns formed by oxidation in the drug-metabolizing microsomal system (DMMS). For each description below, choose the component of the microsomal mixed-function oxidase system with which it is most closely associated ... 

DMMS—drug-metabolizing microsomal system DNA—deoxyribonucleic acid dopa/DOPA/Dopa—(3,4-dlhydroxyphenylalanine)... 

Evidence suggests that endosulfan can induce microsomal enzyme activity. Increased liver microsomal cytochrome P-450 activity was observed in male and female rats after single and multiple administrations of endosulfan (Siddiqui et al. 1987a Tyagi et al. 1984). Increased enzyme activity was observed in hepatic and extrahepatic tissues. Based on the increase in aminopyrine-A-demethylase and aniline hydroxylase activity, endosulfan has been shown to be a nonspecific inducer of drug metabolism (Agarwal et al. 1978). 

Walker, C.H. (1978). Species differences in microsomal monooxygenase activities and their relationship to biological half lives. Drug Metabolism Reviews 7(2), 295-323. 

Walker, C.H. (1980). Species variations in some hepatic microsomal enzymes that metabolise xenobiotics. Progress in Drug Metabolism 5, 118-164. 

Among common in vitro metabolizing systems, liver microsomes and liver S9 fractions are used more often in metabolite synthesis than other systems. The majority of drug metabolism is mediated by CYPs [8]. Liver microsomes contain a high concentration of CYPs and other... 

Fisher, M.B., Campanale, K., Ackermann, B.L. et al. (2000) In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin. Drug Metabolism and Disposition The Biological Fate of Chemicals, 28, 560-566. 

Chauret, N., Gauthier, A. and Nicoll-Griffth, D.A. (1998) Effect of common solvents on in vitro cytochrome P450 mediated metabolic activities in human liver microsomes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 26, 1-4. 

A linear approach to predicting absolute oral bioavailability based on a single parameter, such as rate or extent of absorption (fraction of dose absorbed or estimated dose absorbed) or the rate of metabolism (microsomal or hepatic intrinsic clearance), may result in an inaccurate prediction. The linear approach will not reconcile the bioavailability for highly absorbed and highly metabolized drugs or for poorly absorbed and slowly metabolized drugs. Therefore, if either permeability... 

Sultatos, L.G. and S.D. Murphy. 1983. Hepatic microsomal detoxification of the organophosphates paraoxon and chlorpyrifos oxon in the mouse. Drug Metabol. Dispos. 11 232-238. 

Riviere, J.L., J. Bach, and G. Grolleau. 1983. Effect of pyrethroid insecticides and N-(3,5-dichlorophenyl) dicarboximide fungicides on microsomal drug-metabolizing enzymes in the Japanese quail (Cotumix cotumix). Bull. Environ. Contam. Toxicol. 31 479-485. 

Campbell, M.A., S. Bandiera, L. Robertson, A. Parkinson, and S. Safe. 1983. Hepta-, hexa-, tetra- and dichloronaphthalene congeners as inducers of hepatic microsomal drug-metabolizing enzymes. Toxicology 26 193-205. 

With respect to drug-metabolizing enzymes, the majority of the CYPs responsible for phase I metabolism are concentrated in liver. The CYPs considered here are all found in the endoplasmic reticulum (isolated as microsomes ). Of the 18 human CYP families known, the bulk of xenobiotic biotransformation processes are carried out by enzymes from the CYP1, CYP2 and CYP3 families. In humans, realistically,... 

Sladek, N.E. and Mannering, G.J. (1969) Induction of drug metabolism. I. Differences in the mechanisms by which polycyclic hydrocarbons and phenobarbital produce their inductive effects on microsomal N-demethylating systems. Molecular Pharmacology, 5 (2), 174-185. 

Wienkers, L.C., Allievi, C., Hauer, M.J. and Wynalda, M.A. (1999) Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metabolism and Disposition, 27 (11), 1334-1340. 

Margolis, J.M. and Obach, R.S. (2003) Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502 D6 implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metabolism and Disposition, 31 (5), 606-611. 

Tran, T.H., Von Moltke, L.L., Venkatakrishnan, K., Granda, B.W., Gibbs, M.A., Obach, R.S., Harmatz, J.S. and Greenblatt, D.J. (2002) Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors. Drug Metabolism and Disposition, 30 (12), 1441-1445. 

Substrate-dependent effect of acetonitrile on human liver microsomal cytochrome P450 2C9 (CYP2C9) activity. Drug Metabolism and Disposition, 28 (5), 567-572. 

Palamanda, J., Feng, W.W., Lin, C.C. and Nomeir, A.A. (2000) Stimulation of tolbutamide hydroxylation by acetone and acetonitrile in human liver microsomes and in a cytochrome P-450 2C9-reconstituted system. Drug Metabolism and Disposition, 28 (1), 38-43. 

Fawade MM, Pawar SS. 1983. Effect of NIC12 and cycloheximide on microsomal drug metabolism and ALA-synthetase during thiodemeton toxicity. Indian J Exp Biol 21 343-346. 

Mannering, G.J. Microsomal enzyme systems which catalyze drug metabolism. In La Du, B.N., Mandel, H.G. and Way, E.L. (Eds.) Fundamentals of Drug Metabolism and Disposition. Baltimore, Williams.(1971). 

Bend, J. R., Pohl, R. J., and Fouts, J. R. Some properties of the microsomal drug-metabolizing enzyme system in the little skate, Rada evinaoea. Bull. Mt. Desert Island Biol. Lab. (1972) 12 9-12. 

---