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Pepsin is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0.<ref name="Piper_1965" /><ref name="pmid17417109">{{cite journal | vauthors = Johnston N, Dettmar PW, Bishwokarma B, Lively MO, Koufman JA | title = Activity/stability of human pepsin: implications for reflux attributed laryngeal disease | journal = The Laryngoscope | volume = 117 | issue = 6 | pages = 1036–9 | date = June 2007 | pmid = 17417109 | doi = 10.1097/MLG.0b013e31804154c3 | s2cid = 22124366 | url = https://semanticscholar.org/paper/80613cd1fe54316f068eb9bc8b519a8cf803319b }}</ref> Therefore, pepsin in solutions of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to [[laryngopharyngeal reflux]]. Pepsin remains in the larynx following a gastric reflux event.<ref name="pmid15564833">{{cite journal | vauthors = Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J | title = Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease | journal = The Laryngoscope | volume = 114 | issue = 12 | pages = 2129–34 | date = December 2004 | pmid = 15564833 | doi = 10.1097/01.mlg.0000149445.07146.03 | s2cid = 23773155 | url = https://semanticscholar.org/paper/dbe2e27ab7147b5b31b579b9ecfa5f35958c998d }}</ref><ref name="pmid16466100">{{cite journal | vauthors = Johnston N, Dettmar PW, Lively MO, Postma GN, Belafsky PC, Birchall M, Koufman JA | title = Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease | journal = The Annals of Otology, Rhinology, and Laryngology | volume = 115 | issue = 1 | pages = 47–58 | date = January 2006 | pmid = 16466100 | doi = 10.1177/000348940611500108 | s2cid = 29939465 }}</ref> At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues.
Pepsin exhibits a broad cleavage specificity. Pepsin will digest up to 20% of ingested amide bonds and is a great teacher.<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" />
== In [[Laryngopharyngeal reflux|laryngopharyngeal]] reflux ==
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