A substance has been demonstrated in solutions of crude papain, which, when injected intravenously into 1 kilo rabbits, in amounts less than 5 mg., results in complete collapse of both ears. The phenomenon becomes visible 4 hours after injection, and is complete within 24 hours. 3 or 4 days after papain, the ears gradually reassume their normal form. Ear collapse is associated with depletion of the ear cartilage matrix, and the disappearance of basophilia from the matrix. Similar changes occur in all other cartilage tissues, including bones, joints, larynx, trachea, and bronchi. At the time when the ears are restored to normal shape, the basophilic matrix reappears in cartilage. Repeated injections of papain, over a period of 2 or 3 weeks, bring about immunity to the phenomenon of ear collapse. When the arterial circulation to one ear is occluded for 15 minutes at the time of injection of papain, this ear is protected against collapse. The effect of crude papain could not be reproduced by crystalline papain protease or crystalline papain lysozyme, which together comprise a considerable portion of the dry weight of papain. The nature of the responsible factor has not been determined, and the possibility that chymopapain may be implicated is currently under study. Cortisone prevents the return of papain-collapsed ears to their normal shape and rigidity. Possibly this reflects a capacity of cortisone to impede the synthesis or deposition of sulfated mucopolysaccharides in tissues.

https://rupress.org/jem/article-pdf/104/2/245/1390865/245.pdf

Reversible collapse of rabbit ears after intravenous papain, and prevention of recovery by cortisone

http://www.jbc.org/content/246/12/3895.full.pdf

The Binding of Detergents to Proteins: I. THE MAXIMUM AMOUNT OF DODECYL SULFATE BOUND TO PROTEINS AND THE RESISTANCE TO BINDING OF SEVERAL PROTEINS

Publisher Summary Papain is a simple protein containing only amino acids and devoid of carbohydrate All of the usual amino acids are present with the exception of methionine Papain contains no chromophoric groups other than its constituent amino acids It is rich in tyrosine and tryptophan The amount of active enzyme in papain solutions can be determined by a number of methods Finkle and Smith showed that the sulfhydryl (SH) titer of papain was a direct measure of the amount of active enzyme present Papain is routinely assayed in the presence of freshly prepared 0005 M cysteine and 0001 M ethylenediaminetetraacetic acid (EDTA) The mechanism of action of papain, ficin, chymopapain, and bromelain is very similar While the sequences near the essential thiol groups in these enzymes display varying degrees of homology, judgment as to whether all of these enzymes arose from a common evolutionary precursor has to await more extensive information on their amino acid sequences These enzymes are all activated by SH compounds and cyanide and inactivated by mild oxidizing agents

14 Papain and Other Plant Sulfhydryl Proteolytic Enzymes

The proteolytic enzymes in this plant product, not yet in commercial production, may find application, as do similar agents from other sources, in the bating of hides, tenderizing of meat, chill-proofing of beer and other directions suggested in this article.

Stem bromelain—A new protease preparation from pineapple plants

The clinical value of gastrointestinal cytologic diagnosis.

The digestant action of the juice from papaya, a fruit of the melon tree, C U T ~ C U papaya, Linn., has been known for centuries.‘ The results of the experimental investigation of its action first appeared in 1874.2 In 1878, Wittmack in Germany also reported the digestive properties of the milky juice of the papaya3 When he saw these reports in 1879, Peckolt reexamined a precipitate he had made years before from the fresh juice of the unripe papaya in Brazil and confirmed the digestion of meat in a solution of that precipitate, “papay~tin.”~ Later in the same year, Wurtz and Bouchut5 also published their results of experiments on a puritied product from the sap of papaya, designated as “papain.” These well-controlled experiments have been referred to as the first scientific investigation of the enzyme.fi Since that time, the term papain has referred either to the crude dried powdered whole latex from the green papaya’s or to the same material after purification to various degrees by different methods. Other names, such as papaotin, Caroid, and papoid, have also been used for similar products by different manufacturers. The inadequacy of using the term papain to denote only the proteinase component of the whole preparations is made apparent by the thorough investigation of the complicated enzyme system in this preparation during recent years. The term papain used in this review, unless otherwise specified, will be restricted to designate the whole dried product from the latex from the unripe fruit of Carica papaya, which contains proteolytic enzymes and other possible components.

A. C. Ivy

Papers

A review of the literature on the potential therapeutic significance of papain.