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Papain is a cysteine protease isolated from the latex of the immature fruit and leaves of the plant, Carica papaya. It consists of a single 23.4 kDa, 212 amino acid polypeptide and the purified enzyme exhibits broad proteolytic activity. Although it can be used as a debriding agent, it is also used for a variety of other industrial processes, including meat tenderizing, and for the clarification of beverages.
Collagenase is a protease that can utilize collagen as a substrate. Although it can be produced by animal cell culture, certain microorganisms also produce this enzyme, most notably certain species of Clostridium (the ability of these pathogens to produce collagenase facilitates their rapid spread throughout the body). Collagenase used therapeutically is usually obtained from cell fermentation supernatants of Clostridium histolyticum. Such preparations are applied topically to promote debridement of wounds, skin ulcers and burns.
Chymotrypsin has also been utilized to promote debridement, as well as the reduction of soft tissue inflammation. It is also used in some ophthalmic procedures—particularly in facilitating cataract extraction. It is prepared by activation of its zymogen, chymotrypsinogen, which is extracted from bovine pancreatic tissue.
Yet another proteolytic preparation used for debridement of wounds and skin ulcers consists of proteolytic enzymes derived from Bacillus subtilis. The preparation displays broad proteolytic activity and is usually applied several times daily to the wound surface.
A number of enzymes may be used as digestive aids (Table 9.13). In some instances, a single enzymatic activity is utilized, whereas other preparations contain multiple enzyme activities. These enzyme preparations may be used to supplement normal digestive activity, or to confer upon an individual a new digestive capability.
The use of enzymes as digestive aids is only applied under specific medical circumstances. Some medical conditions (e.g. cystic fibrosis) can result in compromised digestive function due to insufficient production/secretion of endogenous digestive enzymes. Digestive enzyme preparations are often formulated in powder (particularly tablet) form, and are recommended to be taken orally immediately prior to or during meals. As the product never enters the blood
BLOOD PRODUCTS AND THERAPEUTIC ENZYMES 399
Table 9.13. Enzymes that are used as digestive aids
a-Amylase Aids in digestion of starch
Cellulase Promotes partial digestion of cellulose
a-Galactosidase Promotes degradation of flatulance factors
Lactase Counteracts lactose intolerance
Pepsin Enhanced degradation of dietary protein
Pancreatin Enhanced degradation of dietary carbohydrate, fat and protein
stream, the product purity need not be as stringent as enzymes (or other proteins) administered intravenously. Most digestive enzymes are, at best, semi-pure preparations.
In some instances, there is a possibility that the efficacy of these preparations may be compromised by conditions associated with the digestive tract. Most function at pH values approaching neutrality. They would thus display activity possibly in saliva and particularly in the small intestine. However, the acidic conditions of the stomach (where the pH can be below 1.5), may denature some of these enzymes. Furthermore, the ingested enzymes would also be exposed to endogenous proteolytic activities associated with the stomach and small intestine. Some of these difficulties, however, may be at least partially overcome by formulating the product as a tablet coated with an acid-resistant film to protect the enzyme as it passes through the stomach.
Pancreatin is a pancreatic extract usually obtained from the pancrease of slaughterhouse animals. It contains a mixture of enzymes, principally amylase, protease and lipase and, thus, exhibits a broad digestive capability. It is administered orally, mainly for the treatment of pancreatic insufficiency caused by cystic fibrosis or pancreatitis. As it is sensitive to stomach acid, it must be administered in high doses or, more usually, as enteric coated granules or capsules which may be taken directly, or sprinkled upon the food prior to its ingestion. Individual digestive activities, such as papain, pepsin or bromelains (proteases), or a-amylase are sometimes used in place of pancreatin.
Cellulase is not produced in the human digestive system. Cellulolytic enzyme preparations obtained from Aspergillus niger or other fungal sources are available and it is thought that their ingestion may improve overall digestion, particularly in relation to high-fibre diets.