Pepsin function

Trypsin, on the other hand, is destroyed by methylation or deamination, although untreated trypsin is able to attack proteins that have been methylated or deaminated. From this, we conclude that pepsin functions by means of its carboxyl groups interacting with the free amino groups of the protein substrate while trypsin functions by means of its amino groups interacting with the carboxyl groups of the substrate. 

Enzymes Degrading Macromolecules. Enzymes that degrade macromolecules such as membrane polysaccharides, stmctural and functional proteins, or nucleic acids, have all shown oncolytic activity. Treatment strategies include the treatment of inoperable tumors with pepsin (1) antitumor activity of carboxypeptidase (44) cytotoxicity of ribonudease (45—47) oncolytic activity of neuraminidase (48—52) therapy with neuraminidase of patients with acute myeloid leukemia (53) antitumor activity of proteases (54) and hyaluronidase treatment in the management of human soHd tumors (55). 

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

After the food is swallowed, the digestive process continues in the stomach where the food is attacked by stomach acid. In fact, stomach acid is concentrated hydrochloric acid. The hydrochloric acid, along with an enzyme called pepsin, breaks down proteins in the food. Pepsin can only function in the low pH environment of the stomach. The hydrochloric acid is needed to maintain the low pH that pepsin needs to function. 

Mucus is produced by the mucus neck cells and by the surface epithelial cells of the stomach wall. A thick layer of mucus adheres to the wall of the stomach, forming the gastric mucosal barrier. The function of this barrier is to protect the gastric mucosa from injury — specifically, from the corrosive actions of HCl and pepsin. Together with bicarbonate ion released into the lumen of the stomach, mucus neutralizes the acid and maintains the mucosal surface at a nearly neutral pH. 

Serine/threonine kinase activity has been reported in ESP of pepsin-HCl isolated muscle larvae (Arden el al., 1997) and kinase activity was associated with proteins of 70 and 135 kDa. Phosphorylation status is functionally significant for multiple regulatory factors, including those involved in muscle differentiation (Li et al., 1992). Therefore, kinase activity in parasite secretions may be significant in either the muscle or intestinal phases of infection. 

Many extracellular proteins like immunoglobulins, protein hormones, serum albumin, pepsin, trypsin, ribonuclease, and others contain one or more indigenous disulfide bonds. For functional and structural studies of proteins, it is often necessary to cleave these disulfide bridges. Disulfide bonds in proteins are commonly reduced with small, soluble mercaptans, such as DTT, TCEP, 2-mercaptoethanol, thioglycolic acid, cysteine, etc. High concentrations of mercaptans (molar excess of 20- to 1,000-fold) are usually required to drive the reduction to completion. 

The two most important functional constituents of gastric juice, pepsin and hydrochloric acid, are known to vary substantially in concentration from individual to individual. 

For many enzymes, a plot of activity against pH gives a bell-shaped curve with a well-defined pH optimum (Figure 3.8). Most enzymes are adapted to function at the particular pH of their enviromnent and, since the cytosolic pH is about 7.1, most intracellular enzymes have a pH optimum about 7.0. In contrast, the normal pH in the stomach is around 2.0, and most enzymes secreted by cells in the stomach have very low pH optima (e.g. pepsin, whose pH optimum is 2.0). 

Interaction with local tissues. Sucralfate appears to augment the protective function of the mucous-bicarbonate barrier, partly due to increased bicarbonate and mucous secretion, and partly to an interaction with the unstirred layer overlying gastric epithelium, as well as by making the mucous gel more hydrophobic. It binds bile acids and pepsin and adheres to both ulcerated and nonulcerated mucosa. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Powers JC, Harley AD, Myers DV. Subsite specificity of porcine pepsin. In Tang J, ed. Acid Proteases-Structure, Function and Biology. New York Plenum Press, 1977 141-157. 

Figure 7. Emulsifying activity (expressed as volume percentage of the emulsified layer) of pepsin hydrolysates of soy protein as a function of pH and hydrolysis time. No hydrolysis (A) 2 h ( ) 8 h (X) 17 h ( ) 24h(O) (39).

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