Liver metabolic enzyme systems

Donnarumma L, G de Angelis, F Gramenzi, L Vittozzi (1988) Xenobiotic metabolizing enzyme systems in test fish. III. Comparative studies of liver cytosolic glutathione S-transferases. Ecotoxicol Environ Saf 16 180-186. 

The electron transfer system has not been studied in detail in fish, but the metabolism of compounds such as biphenyl (37), benzo(a)pyrene (21) and 2,5-diphenyloxazole (38) by fish liver microsomes has been shown to require oxygen and NADPH generating system. The metabolism of BP (21), 2,5-diphenyloxazole (Ahokas, unpublished observation) and aldrin (27.) by fish liver microsomal enzyme system is inhibited strongly by carbon monoxide. This information and the fact that cytochrome P-1+50, as well as NADPH cytochrome c reductase system are present in fish, suggest strongly that fish have a cytochrome P-1+50 mediated monooxygenase system which is very similar to that described in mammals. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Metabolic transformation to more water-soluble metabolites is necessary for clearance of sedative-hypnotics from the body. The microsomal drug-metabolizing enzyme systems of the liver are most important in this regard, so elimination half-life of these drugs depends mainly on the rate of their metabolic transformation. 

Remmer H (1972) Induction of drug metabolizing enzyme system in the liver. Eur J Clin Pharmacol 5 116-136 Simon P, Chermat R, Doare L et al. (1992) Interactions im-prevues de divers psychotropes avec les effets du barbital et du pentobarbital chez la souris. J Pharmacol 13 241-252... 

Strychnine is rapidly metabolized by the liver microsomal enzyme system requiring NADPH and O2. Five metabolites formed in vitro by rabbit fiver were isolated and identified as 2 -hydroxystrycfinine, 11,12-defiydrostrychnine, strychnine-21, 22-epoxide, 21,22-dihydroxy-22-hydrostrychnine, and strychnine-N-oxide which was the major metabolite and accounted for approximately 15% of the metabolized strychnine. AU other metabolites accounted for less than 1% (Mishimaetfl/., 1985). Similar metabolites were identified in rat urine where the major metabolite was strychnine-21,22-epoxide (Oguri et a/., 1989). The metabolic fate of strychnine in humans is unknown. 

The first-pass effect refers to presystemic elimination by the gut or liver. After being absorbed into enterocytes, compounds can be metabolized by gut and liver metabolic enzymes or effluxed by transporters before they reach the systemic circulation. 

Griseofulvin is detected in the outer layer of the stratum comeum soon after ingestion it is diffused from the extracellular fluid and sweat. There is no information regarding the mechanism by which the drug is delivered to nails and hair. Deposition in the newly formed cells could be the major factor. It is metabolized by the liver microsomal enzyme system and excreted in the urine. Its half-life is 9 to 21 hours. 

The endothelial cells actively, as well as passively, serve to protect the brain. Because they contain a variety of drug-metabolizing enzyme systems similar to the drug-metabolizing enzymes found in the liver, the endothelial cells can metabolize neurotransmitters and toxic chemicals and, therefore, form an enzymatic barrier to entry of these potentially harmful substances into the brain. They actively pump hydrophobic molecules that diffuse into endothelial cells back into the blood (especially xenobiotics) with P-glycoproteins, which act as transmembranous, ATP-dependent efflux pumps. Although lipophilic substances, water, oxygen, and carbon dioxide can readily cross the blood-brain barrier by passive diffusion, other molecules depend on specific transport systems. Differential transporters on the luminal and abluminal endothelial membranes can transport compounds into, as well as out of, the brain. 

Kato R, Takayanaghi M (1966) Differences among the action of phenobarbital, methylcholanthrene and male sex hormone on microsomal drug-metabolizing enzyme systems of rat liver. Jpn J Pharmacol 16 380-390... 

Suresh D, Srinivasan K (2006) Influence of curcumin, capsaicin, and piperine on the rat liver drug-metabolizing enzyme system in vivo and in vitro. Can J Physiol Pharmacol 84 1259-1265... 

Strychnine is rapidly metabolized by the liver microsomal enzyme system and requires NADPH and O2. Five metabolites formed in vitro by rabbit liver were isolated and identified as 2-hydroxystrychnine, 11,12-dehydro-strychnine, strychnine-21,22-epoxide, 21,22-dihydroxy-22-hydrostrychnine, and strychnine-N-oxide, which was... 

Lu, A. Y. H., 1976, Liver microsomal drug-metabolizing enzyme system Functional components and their properties, Ted. Proc. 35 2460. 

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

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