Recent Studies on Insect Hormone Metabolic Pathways Mediated by Cytochrome P450 Enzymes

AbstractObjectivesCytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.MethodsRoma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.ResultsWe found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.ConclusionsThere were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.

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Unraveling the Metabolic Routes of Retapamulin: Insights into Drug Development of Pleuromutilins

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02388-17 ◽

2018 ◽

Vol 62 (4) ◽

Cited By ~ 4

Author(s):

Feifei Sun ◽

Huiyan Zhang ◽

Gerard Bryan Gonzales ◽

Jinhui Zhou ◽

Yi Li ◽

...

Keyword(s):

Cytochrome P450 ◽

Metabolic Pathways ◽

Enzyme Inhibitors ◽

Side Chain ◽

Cytochrome P450 Enzyme ◽

Cytochrome P450 Enzymes ◽

Short Term ◽

P450 Enzyme

ABSTRACT Retapamulin, a semisynthetic pleuromutilin derivative, is exclusively used for the topical short-term medication of impetigo and staphylococcal infections. In the present study, we report that retapamulin is adequately and rapidly metabolized in vitro via various metabolic pathways, such as hydroxylation, including mono-, di-, and trihydroxylation, and demethylation. Like tiamulin and valnemulin, the major metabolic routes of retapamulin were hydroxylation at the 2β and 8α positions of the mutilin moiety. Moreover, in vivo metabolism concurred with the results of the in vitro assays. Additionally, we observed significant interspecies differences in the metabolism of retapamulin. Until now, modifying the side chain was the mainstream method for new drug discovery of the pleuromutilins. This approach, however, could not resolve the low bioavailability and short efficacy of the drugs. Considering the rapid metabolism of the pleuromutilins mediated by cytochrome P450 enzymes, we propose that blocking the active metabolic site (C-2 and C-8 motif) or administering the drug in combination with cytochrome P450 enzyme inhibitors is a promising pathway in the development of novel pleuromutilin drugs with slow metabolism and long efficacy.

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Metabolism of Phytochemicals

10.5772/intechopen.100569 ◽

2021 ◽

Author(s):

Tanu Dixit ◽

Akash Tiwari ◽

Sneha Bose ◽

Himani Kulkarni ◽

Jitendra Suthar ◽

...

Keyword(s):

Cytochrome P450 ◽

Chlorogenic Acid ◽

Gallic Acid ◽

Biological System ◽

Ellagic Acid ◽

Metabolic Pathways ◽

Metabolic Process ◽

Cytochrome P450 Enzymes

Several phytochemicals have been developed as medicinal compounds. Extensive research has recently been conducted on phytochemicals such as curcumin, resveratrol, catechin, gallic acid, humulone, quercetin, rutin, diosgenin, allicin, gingerenone-A, caffeic acid, ellagic acid, kaempferol, isorhamnetin, chlorogenic acid, and others. All of these phytochemicals are metabolized in the biological system. To study the metabolic pathways of phytochemicals, studies are done using both in vitro and in vivo techniques. Metabolism is critical in determining phytochemical bioavailability, pharmacokinetics, and effectiveness. Metabolism can occur in organs such as the intestine, liver, gut, and spleen. The metabolic process is aided by a variety of enzymes, including cytochrome P450 enzymes found in the organs. This study outlines a few phytochemicals metabolic pathways. Tannic acid, ellagic acid, curcumin, quercetin, and resveratrol are selected and explained as examples.

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