Pepsin: Difference between revisions

Pepsin exhibits a broad cleavage specificity. Pepsin will digest up to 20% of ingested amide bonds.<ref name="Lehninger_5th_ed">{{cite book|last1=Cox|first1=Michael|url=https://archive.org/details/lehningerprincip00lehn_1|title=Lehninger principles of biochemistry|last2=Nelson|first2=David R.|last3=Lehninger|first3=Albert L |name-list-style=vanc|publisher=W.H. Freeman|year=2008|isbn=978-0-7167-7108-1|location=San Francisco|url-access=registration |pages = 96}}</ref> Residues in the P1 and P1' positions<ref>The P1 and P1' positions refer to the amino acid residues immediately next to the bond to be cleaved, on the carboxyl and amino side respectively. See {{cite journal | vauthors = Schechter I, Berger A | title = On the active site of proteases. 3. Mapping the active site of papain; specific peptide inhibitors of papain | journal = Biochemical and Biophysical Research Communications | volume = 32 | issue = 5 | pages = 898–902 | date = September 1968 | pmid = 5682314 | doi = 10.1016/0006-291X(68)90326-4 }}</ref> are most important in determining cleavage probability. Generally, hydrophobic amino acids at P1 and P1' positions increase cleavage probability. [[Phenylalanine]], [[leucine]] and [[methionine]] at the P1 position, and [[phenylalanine]], [[tryptophan]] and [[tyrosine]] at the P1' position result in the highest cleavage probability.<ref name="Hamuro_2008" /><ref name="Lehninger_5th_ed" />{{rp|675}} Cleavage is disfavoured by positively charged [[amino acid]]s [[histidine]], [[lysine]] and [[arginine]] at the P1 position.<ref name="Hamuro_2008" />

 

Pepsin is one of the primary causes of mucosal damage during [[laryngopharyngeal reflux]].<ref name="pmid4884956">{{cite journal | vauthors = Goldberg HI, Dodds WJ, Gee S, Montgomery C, Zboralske FF | title = Role of acid and pepsin in acute experimental esophagitis | journal = Gastroenterology | volume = 56 | issue = 2 | pages = 223–30 | date = February 1969 | pmid = 4884956 | doi = 10.1016/S0016-5085(69)80121-6 | doi-access = free }}</ref><ref name="pmid6808683">{{cite journal | vauthors = Lillemoe KD, Johnson LF, Harmon JW | title = Role of the components of the gastroduodenal contents in experimental acid esophagitis | journal = Surgery | volume = 92 | issue = 2 | pages = 276–84 | date = August 1982 | pmid = 6808683 }}</ref> Pepsin remains in the larynx (pH 6.8) following a gastric reflux event.<ref name="pmid15564833"/><ref name="pmid16466100"/> While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events.<ref name="pmid17417109"/> Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage.<ref name="pmid17417109"/><ref name="pmid15564833"/><ref name="pmid16466100"/>