Pepsin

I.U.B.: 3.4.23.1

Pepsin, an acidic protease, is the principal proteolytic enzyme of vertebrate gastric juice. Its inactive precursor, pepsinogen, is produced in stomach mucosa. Historically it is of interest as one of the first enzymes to be crystallized. John H. Northrop crystallized pepsin in 1930, an achievement for which he shared the Nobel Prize in 1946.

There are several minor pepsins designated "B", "C", and "D"; the major component is "A" to which the following data applies. These pepsins are separable chromatographically.

Conversion of pepsinogen to pepsin, which involves releasing a peptide, may be an autocatalytic process involving self-cleavage by the zymogen ( Sanny et al. 1975; Bustin and Conway-Jacobs 1971; Kassell and Kay 1973). Al-JanabiJanabi et al. (1972) indicate the activation to be intermolecular above pH 4. (See Wong et al. 1972). Anderson and Harthill (1973) report that peptides released on activation have pepsin inhibitory activity. The conversion has been investigated by Wang and Edelman (1971); Stepanov et al. (1971); Neumann and Shinitzsky (1971); McPhie (1972), Glick et al. (1986, 1989), and others.

Characteristics of Pepsin from Porcine Stomach:

Molecular weights: Pepsinogen, 41,000 (Arnon and Perlmann, 1963); Pepsin, 35,000± (Bovey and Yanari 1960).

Optimum pH: Approximately 1.0 for such substrates as casein or hemoglobin if the substrate is "native." (Cornish-Bowden and Knowles 1969).

Composition: The structure of porcine pepsin has been reported on by Chen, Tao and Tang (1975); Marciniszyn, Sepulveda, Huang, Lanier and Tang (1975); Sepulveda, Marciniszyn, Liu, and Tang (1975); Morávek and Kostka (1973); Matyash et al. (1973). Some binding and active site studies are as follows: Sachdev et al. (1975 & 1973); Mains et al. (1973); Stepanov et al. (1973); Perlmann and Kerwar (1973); Chen and Tang (1972); Hartsuck and Tang (1972); Nakagawa and Perlmann (1972); Paterson and Knowles (1972); Raju et al. (1972); Trout and Fruton (1969); Greenwell et al. (1969).

Extinction coefficient: = 14.7 (Knowles et al. 1969).

Isoelectric point: pH 1.0 (Bovey and Yanari 1960).

Isoionic point: 2.2-3.0 (Jonsson 1972).

Specificity: Pepsin has a broad range of substrates and demonstrates an esterase activity. See review by Ryle (1970) and also Sachdev and Fruton (1970).

Inhibitors: Substrate-like opoxides (Tang 1971). See Husain et al. (1971), Knowles et al. (1969), and Rich et al. (1985).

Stability: Pepsin is unstable above pH 6.0. Pepsinogen converts to active pepsin below pH 5.0.