Chymotrypsin insulin degradation

For example, enzyme degradation of insulin is known to be mediated by the serine proteases trypsin, a-chymotrypsin, and thiol metalloproteinase insulin-degrading... 

Minkowski tried unsuccessfully to prepare an extract of dog pancreas that would reverse the effect of removing the pancreas—that is, would lower the urinary or blood glucose levels. We now know that insulin is a protein, and that the pancreas is very rich in proteases (trypsin and chymotrypsin), normally released directly into the small intestine to aid in digestion. These proteases doubtless degraded the insulin in the pancreatic extracts in Minkowski s experiments. 

Li, Y., Z. Shao, and A.K. Mitra. 1992. Dissociation of insulin oligomers by bile salt micelles and its effect on alpha-chymotrypsin-mediated proteolytic degradation. Pharm Res 7 864. 

Drags that structurally resemble nutrients such as polypeptides, nucleotides, or fatty acids may be especially susceptible to enzymatic degradation. For example, the proteolytic enzymes chymotrypsin and trypsin can degrade insulin and other peptide drags. In the case of insulin, proteolysis was shown to be reduced by the coadmmistration of carbopol polymers at 1% and 4% (w/v%), which presumably shifted the intestinal pH away from the optimal pH for proteolytic degradation. 

Bai JPF (1995) The involvement of cytosolic chymotrypsin-like, trypsin-like, and cucumsin-like activities in degradation of insulin-like growth factor I by epithelial tissue. J Pharm Pharmacol 47 674—677... 

Degradation in the gut is caused by endogenous proteases such as trypsin and a-chymotrypsin. Entrapment of macromolecules in liposomes results in better protection against proteolysis [30], Since lipid-soluble molecules are absorbed quickly in the gut, it could be expected that liposome delivery will give enhanced absorption by diffusion. However, this problem is not simple, as illustrated by the lack of uptake of liposomes by enterocytes [30,31]. Insulin entrapped in liposomes is absorbed in this way [32],... 

Polyacrylic acid polymers can inhibit luminal degradation of insulin and other large peptides by trypsin and chymotrypsin. They have strong bioadhesive properties, increasing the in situ absorption of insulin [42]. 

The spectrophotometric evidence reviewed above for the binding of a proportion of the phenolic hydroxyl groups of the tyrosine residues of native proteins is supported by work on the action of tyrosinase on proteins. Sizer (1946) found that this enzyme oxidizes the tyrosine residues in native trypsin, pepsin, chymotrypsin, casein, peptone, insulin, and hemoglobin. Native ovalbumin, human and bovine serum albumin, tobacco mosaic virus (nucleoprotein), human y- and bovine /3-globulins, and bovine fibrinogen are not susceptible to tyrosinase, but become so after tryptic digestion. It was shown (Sizer, 1947) that for the proteins which are oxidized by tyrosinase in the native state, the observed reaction does indeed occur with the intact proteins and does not require preliminary degradation to tyrosine peptides or free tyrosine. The kinetics of the oxidation of tyrosine by tyrosinase have been studied spectropho-tometrically (Mason, 1948 etc.). 

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