This critique we addressed the therapeutic efficacy of azathioprine, which can be more regularly applied than TG in clinical practice, in the aspect of its complicated metabolic pathway as a possible web site forthe potent enzymatic activity of bacteria belonging to gut microbiota.Choice of GUT BACTERIAL SPECIES–POTENTIAL CANDIDATES Responsible FOR THE BIOTRANSFORMATION OF AZATHIOPRINEThe chemical structure of particular drugs, in unique their functional groups (like lactones, nitro, azo, sulfhydryl and urea groups), predispose these compounds for metabolic modifications by gut bacteria. As Zimmermann et al. (Zimmermann and ZimmermannKogadeeva, 2019) have pointed out, the drugs metabolized by many of the bacteria (except Proteobacteria) contain a nitro or azo group, that is prone for the reduction in anaerobic metabolism, though drugs which are especially metabolized by Bacteroidetes include ester or amide groups that may be hydrolyzed. Such chemical modifications of drugs by gut microbiota can lead either to their activation, inactivation or perhaps to the toxification (Stojancevi et al., 2014). In UC therapy, a most common instance in the drug biotransformed by gut microbial enzymes is sulfasalazine. The azo bond of prodrug sulfasalazine is attacked by gut bacterial azoreductases, releasing 5-ASA and sulfapyridine. 5-ASA is definitely an active compound even though the latter one particular causes unwanted effects for instance nausea, anorexia and skin rash (Franzin and Stefancic, 2021). As it was demonstrated within the studies described within the previous section, precise gut bacterial species could carry a comprehensive metabolic pathway of 6-MP independently of your host enzymes. Nevertheless, converting azathioprine to 6-MP needs GST enzymatic activity which surely expands the library of possible gut bacterial candidates for the metabolism of azathioprine. Also, the recent study displaying how a drug metabolite developed by a single bacteria species could be a substrate for the biotransformation by a further bacteria species, causing the variable interpatient response to the drug, indicates how important should be to identify the particular species and pathways that metabolize the drug (Rekdal et al.YS-201 Biological Activity , 2019). The enzymes activating and inactivating production of TGNs inside the metabolic pathway of azathioprine which need to be viewed as as the possible target for the gut microbial enzymes are: GST, TPMT, XO/XD, HPRT, IMPDH, GMPS.N1-Methylpseudouridine web So that you can identify bacteria that encode candidate enzymes expected for the metabolism of azathioprine we performed the analysis by reviewing readily available literature and by utilizing publicly available enzyme databases as BRENDA, MetaCyc, National Center for Biotechnology Info (NCBI) protein database and Universal Protein Resource (UniProt).PMID:23290930 In Table 1 we’ve got reviewed the bacteria by the criteria of possession of enzymes which could catalyze the transformation of azathioprine in the gut and contribute to the remedy outcome. The bacteria species addressed in Table 1 will be the members of commensal gut microbiota or pathobionts involved in IBD. As shown in Table 1, potential candidates for microbial structural modifications of azathioprine belong to the phylaFrontiers in Pharmacology | frontiersin.orgApril 2022 | Volume 13 | ArticleLazarevi et al.Gut Microbiota Metabolism of AzathioprineTABLE 1 | Classification of gut bacteria which possess enzymes involved in the metabolic pathway of azathioprine. Phylum Proteobacteria Class Gammaproteobacteria Order Enterobacterales Fam.
