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| Primary information |
|---|
| ID | 15178 |
| Therapeutic ID | Th1570 |
| Protein Name | Pepsin |
| Sequence | >Th1570_Pepsin
MKWLLLLSLVVLSECLVKVPLVRKKSLRQNLIKNGKLKDFLKTHKHNPASKYFPEAAALIGDEPLENYLDTEYFGTIGIGTPAQDFTVIFDTGSSNLWVPSVYCSSLACSDHNQFNPDDSSTFEATSQELSITYGTGSMTGILGYDTVQVGGISDTNQIFGLSETEPGSFLYYAPFDGILGLAYPSISASGATPVFDNLWDQGLVSQDLFSVYLSSNDDSGSVVLLGGIDSSYYTGSLNWVPVSVEGYWQITLDSITMDGETIACSGGCQAIVDTGTSLLTGPTSAIANIQSDIGASENSDGEMVISCSSIDSLPDIVFTINGVQYPLSPSAYILQDDDSCTSGFEGMDVPTSSGELWILGDVFIRQYYTVFDRANNKVGLAPVA
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| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | NA |
| Description | Pepsin is a potent enzyme in gastric juice that digests proteins such as those in meat, eggs, seeds, and dairy products [L2358]. Studies on gastric digestion from 1820-1840 led to the discovery of pepsin as the substance which, in the presence of stomach acid, causes nutrients including meat or coagulated egg whites to dissolve. Soon afterward, it was shown that these protein nutrients were cleaved by pepsin to products called _peptones_ [A32603]. Pepsin is often used as a replacement enzyme for those with pancreatic insufficiency [L2357]. Stimulation of the pancreas and therefore enzymatic digestion of food is a tightly controlled and is a hormonally mediated process. Any changes or conditions affecting metabolic steps for successful digestion and absorption negatively affect pancreatic enzymatic secretion, entry into the intestine, functionality once inside the intestine, and appropriate mixing with foods/nutrients. Many causes of pancreatic insufficiency require that enzyme replacement therapy is started, including cystic fibrosis, pancreatic cancer, acute and chronic pancreatitis, as well as pancreatic surgery [L2357]. Pepsin is approved by the FDA and is used in food at levels not to exceed current good manufacturing practice [L2363]. Interestingly, it has been used as a marker for laryngopharyngeal reflux (LPR), which is a common illness of otolaryngology (ear, nose and throat specialist) visits [A32604]. Interestingly, recent research has suggested that pepsin participates in the digestion of nucleic acids [L2391]. |
| Indication/Disease | Used as a pancreatic enzyme replacement in pancreatic insufficiency [L2357]. It is intended to mimic naturally produced human pepsin [L2360]. Pepsin powder is prepared from the gastric mucosa of pigs, cattle or sheep [L2367]. In the laboratory, it is primarily used for the unspecific hydrolysis of proteins and peptides in acidic media. In addition, it provides limited hydrolysis of native immunoglobulins, yielding biologically active fragments [L2353]. In certain supplements, pepsin may be combined with betaine and HCl (hydrochloric acid) to aid in digestion in various gastrointestinal conditions [L2360], [L2352]. |
| Pharmacodynamics | Pepsin digests protein [L2358]. It classified by the FDA that is characterizing enzyme activity is that of a peptide _hydrolase_ [L2363]. |
| Mechanism of Action | Glands present in the mucous membrane lining of the stomach produce and store an inactive protein named _pepsinogen_. Impulses from the vagus nerve and the hormonal secretions of the hormones _gastrin_ and _secretin_ promote the release of pepsinogen into the stomach, where it is mixed with hydrochloric acid and quickly converted to the active enzyme _pepsin_. The digestive potency of pepsin is highest at the acidic pH of normal gastric juice. In the intestine, the gastric acids are then neutralized, and pepsin is no longer effective [L2358]. Pepsin, the proteolytic enzyme of the stomach is normally responsible for less than 20% of the protein digestion occuring the gastrointestinal tract. It is an endopeptidase enzyme that metabolizes proteins to peptides. It preferentially hydrolyzes peptide linkages where one of the amino acids is aromatic. Pepsin, like other protease enzymes, is produced from an inactive precursor, _pepsinogen_, which is stored in granule form in the chief cells of the stomach and are released by a process called _exocytosis_ [L2362]. In the digestive tract, pepsin activity only contributes to the partial breakdown of proteins into smaller units called peptides, which then either are absorbed from the intestine into the bloodstream or are broken down further by pancreatic enzymes [L2358]. |
| Toxicity | Oral LD50 Rat 90000 mg/kg [MSDS] Chronic backflow of pepsin, acid, and other substances from the stomach into the esophagus, is the basis of reflux conditions, particularly gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux. In the latter, pepsin and acid travel all the way up to the larynx, where they can lead to damage of the laryngeal mucosa and lead to symptoms ranging from hoarseness of the voice and chronic cough to laryngospasm (involuntary contraction of the vocal cords) as well as laryngeal cancer [L2358]. Though limited data is available on the toxicity of exogenous pepsin (not naturally produced in one's gastrointestinal tract), it can be extrapolated from the above-mentioned information that pepsin overdose may lead to mucosal tissue damage of the gastrointestinal tract. |
| Metabolism | Pepsin is the first of several enzymes that digest proteins. In the stomach, polypeptide chains bind in the deep active site groove of pepsin, and are then digested into smaller pieces. Following this, a variety of proteases and peptidases in the intestine complete the process. The small fragments, which are amino acids and dipeptides, are then absorbed by cells for use as metabolic energy or construction of new proteins [L2361]. |
| Absorption | NA |
| NA |
| Clearance | NA |
| Categories | Peptide Hydrolases |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | NA |
| Brand Name | Glutamic Acid Pepsin and Betaine Tablets |
| Company | Jamieson Laboratories Ltd |
| Brand Description | Jamieson Laboratories Ltd |
| Prescribed For | Oral |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |