Liver mixed-function oxygenase

Choice of Tissue. The next choice is that of source tissue. Preparations derived from liver are the most useful, as this tissue is a rich source of mixed-function oxygenases capable of converting procarcinogens to genetically active electrophiles. However,... 

The enzymes appear to be cytochrome Ph50 mixed-function oxygenases with electron transfer components similar to those found in liver (19,20). 

Metabolism of the cyclic diesters retrorsine (166), monocrotaline (169), and crispatine (171) by a variety of mammalian liver microsome preparations and by Peptococcus heliotrinreducans has been reported. Mattocks and co-workers have studied the metabolism of retrorsine by liver microsome preparations from several sources 167-169) and have demonstrated the conversion of this alkaloid to the corresponding iV-oxide 167 and a pyrrolic metabolite formulated as 168. The formation of 168 via 167 and dehydration is mitigated against by the observation that retrorsine TV-oxide (167) does not give rise to a pyrrolic metabolite on incubation with rat liver microsomes 167), even though the enzyme system responsible for the production of 168 from retrorsine has many of the properties of the mixed-function oxygenases capable of N-oxidation 167,174). The metabolites of retrorsine... 

PCN exposure to rats causes enzyme induction in the liver, kidney and lung [250-252]. Mixed-function oxygenases (MFO) are involved in the hydroxyla-tion of xenobiotica. The induction potency of a compound depends on the chlorination degree, substitution pattern and planarity of the molecule. The compounds 3-methylcholanthrene and phenobarbital induce two different... 

The NADPH-cytochrome P-450 system, commonly known as the mixed-function oxygenase (MFO) system, is the most important enzyme system involved in the Phase I oxidation reactions. Cytochrome P-450 system, localized in the smooth endoplasmic reticulum of cells of most mammalian tissues, is particularly abundant in the liver. This system contains a number of isozymes which are versatile in that they catalyze many types of reactions including aliphatic and aromatic hydroxylations and epoxidations,... 

Polybrominated biphenyls (PBBs) were shown to increase the renal toxicity of 1,1,2-trichloroethane as measured by decreases in p-aminohippurate accumulation in renal cortical slices (Kluwe et al. 1978). PBBs are known to increase the activities of microsomal mixed-function oxygenases in the kidney and liver, so increased metabolism of 1,1,2-trichloroethane and the increased presence of metabolites more toxic than the parent compound itself may be responsible for the increased toxicity of 1,1,2-trichloroethane in the kidney. However, the study also showed that PBBs did not increase the hepatotoxic effects of 1,1,2-trichloroethane, as indicated by relative liver weight or SGOT levels. 

Lagos. G. S.. and Cooper, R. R. Electron microscope visualization of proteinpolysaccharides. Clin. Orthop. Relat. Res., 84 179-192, 1972. Leber. H. W., Degkwitz, E-. and Staudinger, H. Studies on the effect of ascorbic acid on the activity and biosynthesis of mixed function oxygenases and on the concentration of haemoproteins in the micro-some fraction of guinea pig liver. Hoppe-Seyler s Z. Physiol. Chem., 350. 439-445.1969. 

Squalen biochemically the most important aliphatic triterpene. M, 408, bLp.ig 262-264°C, p 0.8584. For formula see Triterpenes. S. was first isolated from fish liver oils, and later found in many plant oils. It is the intermediate in the biosynthesis of all cyclic triterpenes. Cyclization of S. is catalysed by a mixed function oxygenase, and proceeds via 23-epo-xysqualene (squalene epoxide). 

In the Ames test (with or without metabolism by extracts of rat livers induced for microsomal mixed-function oxygenases with methylcholanthrene, or Arochlor) 2-4 were inactive at low-medium... 

In mammals, an enzyme system called Mixed Function Oxygenase (MFO) located in the liver and sometimes in several other organs of... 

Most phase one reactions are catalyzed by the drug-metabolizing enzymes (mixed function oxidases, oxygenases) located in the endoplasmic reticulum of liver and, to a lesser extent, in intestine, kidney, and lung. These enzymes have been the subject of intensive research (G7, G8, LI). 

Oxidations. Most oxidative processes take place in liver microsomes and are catalysed by mono-oxygenase enzymes known as mixed-function oxidases. These processes require reduced nicotinamide-adenine dinucleotide phosphate, molecular oxygen and a complex of enzymes in the endoplas-matic reticulum. The terminal oxidizing enzyme is cytochrome P450, a hemoprotein. The notation P450 refers to the ability of the reduced (ferrous) form of the hemoprotein to react with carbon monoxide, yielding a complex with absorption peak at 450 nm. For each molecule... 

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