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A Review on L-Asparaginase
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Many of the investigations focused on the variability in the genetic level in xenobiotic metabolism. The development of ALL may be affected by the DNA repair pathways and functions of cell-cycle checkpoints that might depend on dietary, environmental and other external factors. Although there are a limited number of investigations, reports exist to support a possible role for polymorphisms in the genes that are coding for cytochrome P450, glutathione S-transferases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) quinone oxidoreductase, serine hydroxymethyltransferase, thymidylate synthase and cell-cycle inhibitors.
Renal Drug-Metabolizing Enzymes in Experimental Animals and Humans
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
There are many other pathways of xenobiotic metabolism in the kidney that either cannot be readily classified as phase I or II reactions or, alternatively, have been little studied. This section will highlight some of these alternative pathways.
Gastrointestinal Function and Toxicology in Canines
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems [29–34,123,136,148,202,230,236,263,273,286,296,301,316,364,410]. More generally, xenobiotic metabolism (from the Greek xenos, “stranger” and biotic, “related to living beings”) is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism’s normal biochemistry, such any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds (although in some cases the intermediates in xenobiotic metabolism can themselves cause toxic effects). The study of drug metabolism is called pharmacokinetics.
Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes
Published in Gut Microbes, 2020
Maximillian J. Bailey, Noopur N. Naik, Laura E. Wild, William B. Patterson, Tanya L. Alderete
In addition to altering the composition of the gut microbiota, increased exposure to air pollutants may also modify gut bacterial function, including the production of gut bacterial-derived metabolites involved in biological processes related to obesity and type 2 diabetes.20,102 Indeed, studies have shown that specific gut bacteria are involved in SCFA,103 lipid,104 amino acid,102,108 bile acid,109,110 and tryptophan metabolism,43,111 which have been linked with gut barrier integrity, satiety, body weight, adipose tissue inflammation, and type 2 diabetes. Bacteria in the gut also play an important role in xenobiotic metabolism of environmental toxicants.51,52 For example, the human colon microbiota has been shown to biotransform PAH to estrogenic metabolites,51 which has the potential to modulate pathways related to insulin resistance and obesity.112,113
In vitro sulfonation of 7-hydroxycoumarin derivatives in liver cytosol of human and six animal species
Published in Xenobiotica, 2020
Risto O. Juvonen, Olli Pentikäinen, Juhani Huuskonen, Juri Timonen, Olli Kärkkäinen, Aki Heikkinen, Muluneh Fashe, Hannu Raunio
Interspecies variation of xenobiotic metabolism is commonly, but inadequately known kinetic factor determining differences in effects of chemicals between species (Reichard et al., 2016). Marked interspecies variation in sulfonation rates are known to exist. For example, sulfonation activity is particularly low in pig and high in cat (Coughtrie, 2016; Dalgaard, 2015). Our study, to our best knowledge, is the first to directly compare baseline sulfonation rates in liver cytosol of human, mouse, rat, pig, rabbit, dog and sheep. The results showed that phenolic 7-hydroxycoumarins are sulfonated in all these species, but substantial differences in sulfonation rate and efficiency exists. In dog and rat sulfonation of most of the compounds occurred faster than in other species, while in pig and human sulfonation rate of the compounds was lower in comparison. The substantial variation in sulfonation was illustrated by rates at fixed substrate concentration, and the kinetic parameters Km, Vmax and Vmax/Km varied 2–100 fold (depending on the substrate) among the species. Treatment of mice with inducers of xenobiotic metabolizing enzymes did not affect sulfonation rates.
The potential role of interventions impacting on gut-microbiota in epilepsy
Published in Expert Review of Clinical Pharmacology, 2020
Luigi F Iannone, Maria Gómez-Eguílaz, Rita Citaro, Emilio Russo
On the other hand, the gut microbiome can influence xenobiotic metabolism to modulate efficacy, absorption, and bioavailability, through varied direct and indirect mechanisms on the metabolism of pharmaceuticals and dietary compounds, with both beneficial and potentially harmful outcomes. Direct and indirect mechanisms could be involved with binding of xenobiotics to bacteria, pro-drug activation, enterohepatic cycling, and expression of host hepatic cytochromes P450 (CYP) genes [99]. To date, few studies have been performed involving AEDs and their impact on gut microbiota, with no studies in humans so far (Table 2). In the above-cited paper of Maier et al., among the 16 drugs included in the subgroup N03A (Anatomical Therapeutic Chemical [ATC] classification), that include antiepileptic drugs, no antimicrobial effects have been highlighted [60]. However, clobazam and valproate have shown to be metabolized (the microbiome contributes 78% to systemic amino-clonazepam [NH2-CLZ]) and to influence gut-microbiota composition in animal models (increasing the relative abundance of several species), respectively [100,101]. Valproate has shown to inhibit also Mycobacterium smegmatis in vitro [102]. Lamotrigine and zonisamide have demonstrated in vitro an association with gut microbiota; the first seems to inhibit ribosomal biogenesis in E. coli and the latter is metabolized to 2-sulfamoylacetylphenol by the gut microbiota [103,104].