Gastrointestinal tract enzyme inhibitors

Antidepressants of this class, such as moclobemide, have a high selectivity and affinity for MAO-A. Flowever, unlike the MAOIs, the RIMAs are reversible inhibitors of the enzyme and can easily be displaced from the enzyme surface by any primary amine which may be present in the diet. This means that the dietary amines are metabolized by MAO in the wall of the gastrointestinal tract while the enzyme in the brain and elsewhere remains inhibited. Thus the RIMAs have brought the MAOIs back into use as antidepressants in general practice. It is now evident that the RIMAs are not as potent as most currently available antidepressants. 

NO is also a likely candidate for the NANC messenger of the myenteric plexus of neurons in the gastrointestinal tract, which mediate peristaltic movements. These neurons are rich in NO synthase and inhibitors of this enzyme prevent the nerve-evoked relaxation of the gut [12]. Nitric oxide released from nitroprusside also stimulates ADP ribosylation of glyceradehyde 3-phosphate dehydrogenase [56]. Consequently, there may be a number of enzymes, which are probably Fe-centered, that may be activated by NO. 

Why this elaborate mechanism for getting active digestive enzymes into the gastrointestinal tract Synthesis of the enzymes as inactive precursors protects the exocrine cells from destructive proteolytic attack. The pancreas further protects itself against self-digestion by making a specific inhibitor, a protein called pancreatic trypsin inhibitor (p. 231), that effectively prevents... 

Acarbose (1) is a stable transition state inhibitor of this reaction. Its structure resembles the transition state structure of the polysaccharide, although it lacks the ability to form a stable oxonium ion intermediate. Acarbose (1) has a 105-fold higher affinity than typical substrates. Thus, it binds the a-gluco-sidase enzyme, incapacitating it from its action on its normal substrates. This prevents the release of monosaccharides from polysaccharides in the stomach and intestine. The normal polysaecharides that are usually broken down in the gastrointestinal tract are eliminated in feces. 

As mentioned above, the oral administration of peptides often results in very low bioavailability due to poor membrane penetration characteristics (transport barrier) and extensive hydrolysis of peptides by digestive enzymes of the gastrointestinal tract (enzymatic barrier) [1]. Of these two barriers, the latter is of great importance for certain unstable small peptides, as these peptides can be transported across the intestinal membrane unless they are degraded by proteases. Thus, the use of protease inhibitors, if effective at the absorption site, might represent a promising approach to overcome delivery problems associated with peptides and protein biopharmaceuticals. 

Probiotic bacteria differ on the basis of genus, species, and strains. Indeed, strains of the same species vary widely in traits such as expression of enzymes, types of inhibitors produced, carbohydrate fermentation patterns, resistance to acid and bile, ability to colonize the gastrointestinal tract, and clinical efficacy (Berg, 1996 Norat et al., 2002). Furthermore, the active principle has not always been associated with live bacteria, as some immune system modulation activities and macromolecular degradation have been linked to nonviable bacterial components such as enzyme activities or fermentation products (Huttner and Bevins, 1999). 

Dietary fiber is only one of several possible pharmacologically active substances found in foods, and present in high concentrations in leguminous seeds which may be responsible for the different rates of digestion and blood glucose responses of different meals. Enzyme inhibitors, lectins and saponins are other so called antinutritional factors, also associated with dietary fiber which are able to alter small intestinal function (48). The gastrointestinal tract evolved to deal with these constituents in foods so that while toxic in large amounts (as in uncooked beans) small amounts may have beneficial effects. 

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