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PubMed Journals Articles About "Stereoselective Ketamine Metabolism Genetic Variants Cytochrome P450 CYP2B6" RSS

19:24 EDT 24th March 2019 | BioPortfolio

Stereoselective Ketamine Metabolism Genetic Variants Cytochrome P450 CYP2B6 PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Stereoselective Ketamine Metabolism Genetic Variants Cytochrome P450 CYP2B6 articles that have been published worldwide.

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Showing "Stereoselective Ketamine Metabolism Genetic Variants Cytochrome P450 CYP2B6" PubMed Articles 1–25 of 13,000+

Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection.

The cytochrome P450 CYP2B6*6 (CYP2B6 c.516G > T; rs3745274) is one of the genetic factor that alters the drug metabolism in antimalarial, antiretroviral and TB first-line drugs. In Central African populations, the distribution of the CYP2B6*6 variant is poorly documented. This study investigated on the distribution of CYP2B6 c.516G> T variant among Congolese individuals.


From electrochemistry to enzyme kinetics of cytochrome P450.

This review is an attempt to describe advancements in the electrochemistry of cytochrome P450 enzymes (EC 1.14.14.1) and to study molecular aspects and catalytic behavior of enzymatic electrocatalysis. Electroanalysis of cytochrome P450 demonstrates how to translate theoretical laws and equations of classical electrochemistry for the calculation of the kinetic parameters of enzymatic reactions and then translation of kinetic parameters to interpretation of drug-drug interactions. The functional significance...

Cytochrome P450 1A1, 2C9, 2C19, and 3A4 polymorphisms account for inter-individual variability of toxicological drug metabolism in cynomolgus macaques.

Cytochromes P450 (P450s) and their genetic variants in humans are important drug-metabolizing enzymes partly accounted for inter-individual variations in drug metabolism and toxicity. However, these genetic variants in P450s have not been fully investigated in cynomolgus macaques, a non-human primate species widely used in toxicological studies. In this study, genetic variants found in cynomolgus CYP1A1, CYP2C9 (formerly CYP2C43), CYP2C19 (CYP2C75), and CYP3A4 (CYP3A8) were assessed on functional importance...


In vitro and in vivo correlation of hepatic fraction of metabolism by P450 in dog.

1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450 mediated oxidation and UDP-glucuronosyltransferases (UGT) m...

Genetic Variation in Cytochrome P450 2R1 and Vitamin D Binding Protein Genes are associated with Vitamin D Deficiency in Adolescents.

Genome Wide Association Studies (GWAS) have evaluated several genes related to vitamin D synthesis, metabolism and transport. They have proposed a genetic basis for low levels of vitamin D in the blood. The current study aims to investigate the relationship between certain vitamin D-associated gene variants and vitamin D deficiency in Iranian adolescents.

Computational Methods and Tools to Predict Cytochrome P450 Metabolism for Drug Discovery.

In this review we present important, recent developments in the computational prediction of cytochrome P450 (CYP) metabolism in the context of drug discovery. We discuss in silico models for the various aspects of CYP metabolism prediction, including CYP substrate and inhibitor predictors, site of metabolism predictors (i.e. metabolically labile sites within potential substrates) and metabolite structure predictors. We summarise the different approaches taken by these models, such as rule-based methods, mac...

Functional expression of two NADPH-cytochrome P450 reductases from Siraitia grosvenorii.

Cytochrome P450 reductase (CPR) is the redox partner of various P450s involved in primary and secondary metabolism. Here, we identified and characterized two paralogs of cytochrome P450 reductase from Siraitia grosvenorii. There were two full-length CPR isoforms in the S. grosvenorii fruit transcriptome dataset. They had the same open reading frames of 2, 124 bp, encoding 707 amino acids. A phylogenetic analysis characterized both SgCPR1 and SgCPR2 as Class II dicotyledonous CPRs. The recombinant proteins...

Identification of the cytochrome P450 involved in the degradation of neonicotinoid insecticide acetamiprid in Phanerochaete chrysosporium.

We previously reported that cytochrome P450 s play critical roles in neonicotinoid insecticide biodegradation by white-rot fungi. Here, we investigated the biodegradation of acetamiprid (ACET) by Phanerochaete chrysosporium to identify the cytochrome P450 involved in this degradation process. During a 20-day incubation period, P. chrysosporium degraded 21% and 51% of ACET in ligninolytic and nonligninolytic media, respectively. The degradation rate of ACET was markedly decreased by the addition of cytochr...

SMARTCyp 3.0: Enhanced cytochrome P450 site-of-metabolism prediction server.

Cytochromes P450 (CYPs) are the most important class of drug metabolizing enzymes. Prediction of drug metabolism is important in development of new drugs, to understand and reduce adverse drug reactions (ADRs) and to reduce animal testing.

No clinically relevant interactions of St. John's wort extract Ze 117 low in hyperforin with cytochrome P450 enzymes and P-glycoprotein.

Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 enzymes and P-glycoprotein, presumably caused by hyperforin. In a phase I, open-label, non-randomized, single-sequence study, the low-hyperforin Hypericum extract Ze 117 was investigated using a drugs cocktail in 20 healthy volunteers. No pharmacokinetic interactions of Ze 117 were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4 a...

Evaluation of the inhibition effects of apatinib on human and rat cytochrome P450.

Apatinib, a small molecule anti-angiogenic drug, is proven to be safe and effective for treatment of advanced gastric cancer (AGC). It is also a single drug that significantly prolongs survival after failure of standard chemotherapy for AGC, which has attracted the research interest. The purpose of this study is to evaluate the inhibition effects of apatinib on human and rat cytochrome P450, including CYP3A2/4, CYP2B1/6, CYP2C9/11, CYP2D1/6, and CYP2E1. The IC and IC-shift results indicated that apatinib mi...

A new approach to understanding structure-function relationships in cytochromes P450 by targeting terpene metabolism in the wild.

A strategy for elucidating sequence determinants of function in the class of cytochrome P450 (CYP) enzymes that catalyze the first steps of terpene metabolism in wild microbiomes is described. Wild organisms that can use camphor, terpineol, pinene and limonene were isolated from soils rich in coniferous waste. Cell free extracts and growth beers were analyzed by gas chromatography/mass spectrometry to identify primary oxidative metabolites. For one organism, Pseudomonas nitroreducens TPJM, a cytochrome P450...

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat.

Surgical removal of complicated liver tumors may be realized in two stages via selective portal vein ligation, inducing the atrophy of portally ligated lobes and the compensatory hypertrophy of nonligated liver lobes. Unlike morphological changes, functional aspects such as hepatic cytochrome P450 (CYP)-mediated drug metabolism remain vaguely understood, despite its critical role in both drug biotransformation and hepatic functional analysis. Our goal was the multilevel characterization of hepatic CYP-media...

In vivo phenotyping of cytochrome 450 isoforms involved in the metabolism of anti-HIV and anti-tubercular drugs in human using cocktail approach: An LC-MS/MS analysis.

In vivo phenotyping of CYP isoforms involved in the metabolism of anti-HIV and antitubercular drugs is important to determine therapeutic dose levels in HIV/AIDS-TB coinfections. In this study, we used a cocktail of bupropion, losartan and dapsone for in vivo phenotyping of CYP2B6, CYP2C9 and N-acetyltransferase-2 (NAT2) in plasma. CYP2B6 is the main catalyst of anti-HIV efavirenz, while NAT2 is involved in antitubercular drug isoniazid metabolism. CYP2C9 has a significant association with antitubercular dr...

Application of hepatic cytochrome b/P450 reductase null (HBRN) mice to study the role of cytochrome b in the cytochrome P450-mediated bioactivation of the anticancer drug ellipticine.

The anticancer drug ellipticine exerts its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. The present study has examined the role of cytochrome P450 oxidoreductase (POR) and cytochrome b (Cyb5), electron donors to P450 enzymes, in the CYP-mediated metabolism and disposition of ellipticine in vivo. We used Hepatic Reductase Null (HRN) and Hepatic Cytochrome b/P450 Reductase Null (HBRN) mice. HRN mice have POR deleted specifically in hepatocytes; HBRN mice also have Cyb5 delete...

Methadone Metabolism And Drug-Drug Interactions: In Vitro And In Vivo Literature Review.

Methadone is utilized for the treatment of individuals with opiate dependence. Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9 and CYP2C8. In vivo, polymorphism effects on methadone systemic exposure have been noted for CYP2B6, CYP3A4 and CYP2D6. Clinical drug interaction studies with antiviral drugs in methadone maintenance treatment patients yield varying results on methadone pharmacokinetics and pharmacodynamics. In general, ...

In vitro subcellular characterization of flunixin liver metabolism in heifers, steers, and cows.

The majority of cattle found to have violative liver residues of flunixin (FNX) in the United States are dairy cows. It has been hypothesized that illness of cows decreases the rate of FNX metabolism, resulting in violative residues at slaughter. Another contributing factor might be an age-related decrease in FNX metabolism, as dairy cull cows are typically older at slaughter than cattle raised for beef, rather than milk production. In order to investigate this possibility, subcellular fractions were prepar...

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes.

Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer effects. Although there are in vitro studies showing that myricetin inhibits human cytochrome P450 (CYP) 2D6 and CYP3A, the inhibitory mechanisms of myricetin on CYP enzymes are still unclear. The aim of this study was to evaluate the inhibitory effects of myricetin on human and rat CYPs, including CYP3A2/3A4...

The characterisation of two members of the cytochrome P450 CYP150 family: CYP150A5 and CYP150A6 from Mycobacterium marinum.

Actinobacteria, including the Mycobacteria, have a large component of cytochrome P450 family monooxygenases. This includes Mycobacterium tuberculosis, M. ulcerans and M. marinum, and M. vanbaalenii. These enzymes can abstract CH bonds and have important roles in natural product biosynthesis.

Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase.

NADH cytochrome b reductase mediates electron transfer from NADH to cytochrome b utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome b is an important cofactor in many metabolic reactions including cytochrome P450-mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism, hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling of a variety of quinones gener...

Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants.

Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent K, K, and V of 67.2 μM, 12.6 μM, and 1.33 μM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6 activities, a significant correlation was ...

Substrate-induced conformational change in cytochrome P450 OleP.

The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition experienced upon binding by the P450 OleP, an epoxygenase involved in oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized in 2 forms: one with an ensemble of open and closed conformations in the asymmetric unit and another with only the closed conformation. Characterization of OleP-6DEB binding kinetics, also using the P450...

Cytochrome P450 Enzymes and Their Roles in the Biosynthesis of Macrolide Therapeutic Agents.

The study of the genus is of particular interest because it produces a wide array of clinically important bioactive molecules. The genomic sequencing of many species has revealed unusually large numbers of cytochrome P450 genes, which are involved in the biosynthesis of secondary metabolites. Many macrolide biosynthetic pathways are catalyzed by a series of enzymes in gene clusters including polyketide and non-ribosomal peptide synthesis. In general, P450 enzymes accelerate the final, post-polyketide syn...

Porcine cytochrome 2A19 and 2E1.

Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in humans. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summ...

Exploratory genome-wide association analysis of response to ketamine and a polygenic analysis of response to scopolamine in depression.

Growing evidence suggests that the glutamatergic modulator ketamine has rapid antidepressant effects in treatment-resistant depressed subjects. The anticholinergic agent scopolamine has also shown promise as a rapid-acting antidepressant. This study applied genome-wide markers to investigate the role of genetic variants in predicting acute antidepressant response to both agents. The ketamine-treated sample included 157 unrelated European subjects with major depressive disorder (MDD) or bipolar disorder (BD)...


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