Search results for "Microsoma"

Die physiologischen Wirkungen erhitzter Fette, insbesondere der Fritierfette

1973

Die chronische Aufnahme von stark in Gegenwart von Luft thermisch behandelten Fetten („overheated fats”) fuhrt im Tierversuch zu Gesundheitsschadigungen, deren Schwere von der thermischen Belastung abhangig ist. Dagegen hat sich weder in den Untersuchungen anderer Autoren noch in unseren eigenen ein nachteiliger Einflus des Verzehrs von Fritierfetten im Tierversuch nachweisen lassen, vorausgesetzt, das die Verarbeitung der Fette im Sinne einer „good manufacturing practice” erfolgte. Durch das Fritieren erfolgt eine Abnahme des Gehaltes der Fette an den polycyclischen cancerogenen Kohlenwasserstoffen. Ferner bewirken solche Fette eine Induktion mikrosomaler Enzyme, was einen gewissen Schutz …

Genotoxicity characteristics of reverse diol-epoxides of chrysene.

2017

Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his- Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be …

Isoenzyme-specific phosphorylation of cytochromes P-450 and other drug metabolizing enzymes.

1987

Abstract A series of fourteen cytochrome P-450 isoenzymes was treated with three different protein kinases and found to devide into isoenzymes phosphorylated (i) by both the cyclic AMP-dependent kinase and the calcium-phospholipid-dependent kinase (P-450 PB 3a and PB 2e), (ii) by none of these kinases (P-450 PB 1b, MC 1b, UT 1, and thromboxane synthase), and (iii) by either the cyclic AMP-dependent kinase (P-450 LM 2, PB 2d, and PB 3b) or the calcium-phospholipid-dependent kinase (P-450 PB 1a, PB 2a, MC 1a, LM 3c, and LM 4). Other components of the monooxygenase system, cytochrome P-450 reductase, cytochrome b5, cytochrome b5 reductase as well as microsomal epoxide hydrolase, were poor subs…

An insect juvenile hormone-specific epoxide hydrolase is related to vertebrate microsomal epoxide hydrolases.

1996

Abstract We describe the first cDNA sequence encoding a juvenile hormone-specific epoxide hydrolase from an insect. A full-length cDNA clone revealed a 462-amino-acid open reading frame encoding an amino acid sequence with 44% identity and 64% similarity to human microsomal epoxide hydrolase. All residues in the catalytic triad (residues Asp 227 -His 428 -Asp 350 in the M. sexta protein) were present, as was the conserved Trp 154 corresponding to the oxyanion hole. The surprising similarity of insect juvenile hormone epoxide hydrolase to vertebrate microsomal epoxide hydrolases, coupled with the ancient lineage of the epoxide hydrolases and haloalkane dehalogenases, suggests that this catab…

Lomitapide: a novel drug for homozygous familial hypercholesterolemia

2014

Lomitapide (Juxtapid® and Lojuxta®; Aegerion Pharmaceuticals, Inc., MA, USA), an orally administered inhibitor of the microsomal triglyceride transfer protein, inhibits the synthesis and secretion of ApoB-containing lipoproteins and, thus, reduces plasma levels of LDL cholesterol (LDL-C). Lomitapide has been approved for the therapy of homozygous familial hypercholesterolemia patients. After a proof-of-concept Phase II trial, lomitapide has been tested in a multinational single-arm, open-label, 78-week, Phase III trial. Lomitapide effectively reduced mean plasma LDL-C levels by 50% from baseline in 23 adults with homozygous familial hypercholesterolemia over a 26-week treatment period and t…

Mechanisms of Toxification and Detoxification which Challenge Drug Candidates and Drugs

2007

Almost all drugs are metabolized in the human organism. In most cases this changes the toxicity, sometimes by toxification, sometimes by detoxification. For obvious ethical reasons, the toxicity cannot be experimentally studied in human beings. In systems available for toxicity studies such as whole animals or human or animal cells in culture, the drug metabolism is substantially different from that in the human organism. Risk assessment for human therefore requires knowledge of drug metabolism, its differences between systems, and the consequences for toxicity. In phase 1 of drug metabolism (oxidoreductions and hydrolyses) drugs are often toxified. This is especially the case if the result…

Therapeutic options for homozygous familial hypercholesterolemia: the role of Lomitapide

2020

Background:Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine.Aims:The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH.Results:The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol …

‘Threshold effect’ of increasing tocopherol ingestion upon the microsomal epoxide hydrolase activity of rat liver

1990

Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons

1980

Mouse liver cytosol epoxide hydrolase, known to be very active for certain alkene oxides, had a specific activity which was 2.1-, 11- and 160-fold lower than that of the microsomal epoxide hydrolase for the arene oxides 7-methylbenz[a]anthracene 5,6-oxide, benz[a]anthracene 5,6-oxide and phenanthrene 9,10-oxide, respectively. For benzo[a]pyrene 4,5-oxide no activity (less than 10 pmol product/mg protein/min) of cytoplasmic epoxide hydrolase was detectable. The specific activity of cytoplasmic epoxide hydrolase was much lower for all K-region epoxides investigated, compared to trans-stilbene oxide used as a positive control and for which a new assay is described. It is concluded from these r…

Evidence for Several Hepatic Proteins Related to Microsomal Epoxide Hydrolase

1989

Epoxide hydrolases catalyze the conversion of epoxides, some of which have been shown to be carcinogenic, to dihydrodiols (Guenthner and Oesch 1981). At least three forms of epoxide hydrolases exist in rats, two of which, namely mEHb and mEHch, are associated mainly with the microsomal fraction (Oesch et al 1984; Levin et al 1983) whereas one form namely cEH is found to a large extent in the cytosolic fraction (Gill and Hammock 1981). These three forms differ in their immunological and catalytic properties quite considerably (Guenthner et al 1981). In the case of mEHb the existence of several closely related isoenzymes with an identical apparent subunit molecular weight (Mrs) of 50,000 was …