Gastrointestinal tract proteolysis

This occurs in the seromucous secretions such as saliva, tears, nasal secretions, sweat, colostrum and secretions of the lung, urinogenital and gastrointestinal tracts. Its purpose appears to be to protect the external surfaces of the body from microbial attack. It occurs as a dimer in these secretions but as a monomer in human plasma, where its function is not known. The function of IgA appears to be to prevent the adherence of microorganisms to the surface ofmucosal cells thus preventing them entering the body tissues. It is protected from proteolysis by combination with another protein—the secretory component. 

Their low metaholic stability toward proteolysis in the gastrointestinal tract and in serum. 

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Protein catabolism begins with hydrolysis of the covalent peptide bonds that link successive amino acid residues in a polypeptide chain (fig. 22.3). This process is termed proteolysis, and the enzymes responsible for the action are called proteases. In humans and many other animals, proteolysis occurs in the gastrointestinal tract this type of proteolysis results from proteases secreted by the stomach, pancreas, and small intestine. 

The site of administration also influences their pharmacokinetic behavior. Following SC or IM administration, the bioavailability of biopharmaceuticals is often lower than with small molecules due to proteolysis during interstitial and lymphatic transit. Oral delivery of biopharmaceuticals is limited by barriers such as enzymatic and pH-dependent degradation in the gastrointestinal tract, low epithelial permeability, and instability under formulation conditions. Therefore biopharmaceuticals have an extremely low (<1%) and erratic bioavailability after oral administration [3]. 

About 7% of dietary riboflavin is covalently bound to proteins (mainly as riboflavin-8-a-histidine or riboflavin-8-a-cysteine). The riboflavin-amino acid complexes released by proteolysis are not biologically available although they are absorbed from the gastrointestinal tract, they are excreted in the urine (Chia et al., 1978). 

Both avidin and the avidin-biotin complex are very stable to heat. To release biotin from avidin binding, autoclaving above 130°C is required, and free avidin is stable up to about 85°C. Avidin is also resistant to proteolysis and, as is obvious from the use of raw egg white diets to induce biotin deficiency, biotin cannot be released from avidin binding in the gastrointestinal tract. Lysosomal hydrolases do release biotin from avidin binding, and intravenously administered avidin-biotin can be a source of biotin. 

Already most bioactive peptides have been prepared in larger quantities and made available for pharmacological and clinical investigations. Subsequently it became clear that the use of peptides as drugs is limited by the following factors a) their low metabolic stability towards proteolysis in the gastrointestinal tract and in serum b) their poor transport from the gastrointestinal tract to the blood as... 

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