Colon hydrolytic enzymes

Redox reaetions and hydrolysis are the predominant metabolie eonversions triggered by the intestinal microflora. The main reductive enzymes produeed by the intestinal mieroflora are nitroreductase, deaminase, urea dehydroxylase, and azoreduetase the hydrolytic enzymes are P-glucoronidase, P-xylosidase, P-galaetosidase, and a-L-arabinosidase. Studies conducted by Macfarlane and co-workers have shown that proteolysis ean also happen in the colon [31]. More recent findings by this group indieate that bacterial fermentation of proteins in humans could account for 17% of... 

The bacteria in the intestinal tract serve as another well-known source of luminal drug degradation [61], though this is only important for the colon region as the luminal concentration of bacteria is 104 to 109-fold higher in the colon compared with the small intestine. Thus, this aspect is only relevant for drugs that reach this region, for example, due to poor permeability, slow dissolution or delivery by modified-release formulations. Hydrolytic and other reductive reactions are predominantly mediated by bacterial enzymes, and a list of the most prominent types... 

Table 3 Drug metabolizing enzymes in the colon that catalyze hydrolytic reactions...

Analysis of human CE by Northern blot shows a single band of approximately 2.1 kilobases (kb) (Riddles et al. 1991), and three bands of approximately 2-, 3-, and 4.2-kb occurring with hCE-2 (Schwer et al. 1997). The intensities of the 2.1-kb band were liver 3> heart > stomach > testis > kidney = spleen > colon > other tissues. For hCE-2, the 2-kb band was located in liver > colon > small intestine > heart, the 3-kb band in liver > small intestine > colon > heart, and the 4.2-kb band in brain, testis, and kidney only. Analysis of substrate structure versus efficiency for ester (pyrethroid substrates) revealed that the two CEs recognize different structural features of the substrate (i.e., acid, alcohol, etc.). The catalytic mechanism involves the formation of an acyl-enzyme on an active serine. While earlier studies of pyrethroid metabolism were primarily performed in rodents, knowledge of the substrate structure-activity relationships and the tissue distribution of hCEs are critical for predicting the metabolism and pharmacokinetics of pesticides in humans. Wheelock et al. (2003) used a chiral mixture of the fluorescent substrate cyclopro-panecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, cyano(6-methoxy-2-naphthalenyl)methyl ester (CAS No. 395645-12-2) to study the hydrolytic activity of human liver microsomes. Microsomal activity against this substrate was considered to be low (average value of ten samples 2.04 0.68 nmol min mg ), when compared to p-nitrophenyl acetate (CAS No. 830-03-5) at 3,700 2,100 mg ... 

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