pepsin, the powerful enzyme in gastric juice that digests proteins such as those in meat, eggs, seeds, or dairy products.
Pepsin was first recognized in 1836 by the German physiologist Theodor Schwann. In 1930 it was crystallized and its protein nature established by John H. Northrop of the Rockefeller Institute for Medical Research.
Glands in the mucous-membrane lining of the stomach make and store an inactive protein called pepsinogen. Impulses from the vagus nerve and the hormonal secretions of gastrin and secretin stimulate the release of pepsinogen into the stomach, where it is mixed with hydrochloric acid and rapidly converted to the active enzyme pepsin. The digestive power of pepsin is greatest at the acidity of normal gastric juice (pH 1.5–2.5). In the intestine the gastric acids are neutralized (pH 7), and pepsin is no longer effective.
In the digestive tract pepsin effects only partial degradation 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.
Small amounts of pepsin pass from the stomach into the bloodstream, where it breaks down some of the larger, or still partially undigested, fragments of protein that may have been absorbed by the small intestine.
Pepsin is prepared commercially from swine stomachs. Crude pepsin is used in the leather industry to remove hair and residual tissue from animal hides prior to their being tanned. It is also used in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver compound. * Worthington Biochemical Corporation - Pepsin Pepsin is the principal proteolytic enzyme of vertebrate gastric juice. Its inactive precursor form, pepsinogen, is produced in stomach mucosa. The minor pepsins are designated “B”, “C”, and “D”, while the major component is “A”, to which the following data applies.
History:
Pepsin is of particular interest as it was the first enzyme to be discovered. The name pepsin was given by Theodor Schwann (1810-1882) in 1836, and came from pepsis, the term for digestion in Hippocratic writings. Into the mid-nineteenth century, scientists showed that pepsin broke down proteins into “peptones” (Fruton 2002).
Pepsin was later found to be an effective treatment for digestive disorders. Through this important application, efforts to produce and purify it greatly increased, and were successful by the end of the nineteenth century (Tang 1998).
At that time, however, the chemical nature and properties of enzymes as proteins were not completely understood. It was not until John H. Northrop crystallized pepsin in 1930, an achievement for which he shared the Nobel Prize in 1946, that the protein nature of enzymes was established (Manchester 2004).
After the Nobel Prize was awarded to Northrop, Sumner, and Stanley in 1946, new separation methods including crystallization and chromatography were further developed. Through these methods, the amino acid sequences of pepsin and pepsinogen were determined (Tang 1973).
Pepsin B and C were first isolated from porcine stomach by Ryle and Porter in 1959.
As X-ray diffraction techniques improved through the mid-1970s, the three-dimensional structure of pepsin was determined, allowing for a better understanding of the catalytic reaction (Fruton 2002).
Recently, interest in pepsin-type enzymes and their inhibitors has been renewed due to the recognition of HIV-protease as a member of this aspartic protease family (Campos 2003).
Specificity:
Pepsin has broad specificity with a preference for peptides containing linkages with aromatic or carboxylic L-amino acids. It preferentially cleaves C-terminal to Phe and Leu and to a lesser extent Glu linkages. The enzyme does not cleave at Val, Ala, or Gly.
Composition:
Pepsin is a monomeric, two domain, mainly beta protein with a high percentage of acidic residues. Porcine pepsin has 4 basic residues, and 42 acidic residues and is O-phosphorylated at S68 (Tang et al. 1973). For the protein to be active, one of the two aspartate residues in the catalytic site has to be protonated, and the other deprotonated. This occurs between pH 1 and 5, and above pH 7 pepsin is irreversibly denatured.
Molecular Characteristics:
The amino acid sequence of porcine pepsin was determined by Tang et al. (1973) and Moravek and Kostka (1974), and later confirmed through cDNA analysis by Tsukagoshi et al. (1988) and Lin et al. (1989).
The pepsinogen A (PGA) gene is divided among nine exons that encompass approximately 9.4 kb of genomic DNA (Sogawa 1983).
There are multiple versions of the PGA genes found in human and chimp populations, but the activities of these various gene products are indistinguishable (Taggart 1985 and Zelle 1988). In contrast, Southern blot analyses of a sampling of pigs suggest that there is only a single PGAgene found in all pigs (Evers 1988).
PGA production is mainly controlled at the transcription level (Sogawa et al. 1981 and Ichinose et al. 1988). In both humans and pigs, it has been found that the PGA gene is under tissue-specific transcriptional control, with mRNA only detected in gastric fundic mucosa (Ichinose 1991 and Meijerink et al. 1993). Transcription of the PGA gene is regulated by transcription-activating proteins acting at 3 major regions in the promoter and initiation regions of the PGA gene (Meijerink et al. 1993).
There are four reported pepsin proteins: pepsin A, pepsin B (parapepsin I), pepsin C (gastricsin), and pepsin D (an unphosphorylated version of pepsin A) (Lee and Ryle 1967). Pepsin A is the predominant gastric protease; minor amounts of the other pepsins have been detected. Pepsins B and C share a higher degree of homology with each other. In dog, B and C share 89% identity, A and B share 44% identity, and A and C share 45% identity (calculated based on Thompson et al. 1994).
Protein Accession Number: P00791
CATH Classification (v. 3.2.0): * Class: Mainly beta * Architecture: Beta Barrel * Topology: Cathepsin D, subunit A; domain 1
Molecular weight: * Pepsin: 34.5 kDa (Theoretical) * Pepsinogen: 41.4 kDa
Optimal pH: 1.0-4.0 (At pH 1.5 pepsin exhibits about 90% of maximum activity, and at pH 4.5 about 35% of maximum activity.
Isoelectric Point: 1.0 (Bovey and Yanari 1960)
Extinction Coefficient: * 49,650 cm-1 M-1 (Theoretical) * E1%,280 = 14.39 (Theoretical)
Active Site Residues: * Aspartic acid (D32 and D215)
Activators:
* Pepsinogen
Inhibitors:
* Aliphatic alcohols * Substrate-like epoxides * Pepstatin A
Applications:
* Digestion of antibodies * Preparation of collagen for cosmeceutical purposes * Assessment of digestibility of proteins in food chemistry * Subculture of viable mammary epithelial cells (Riser 1983) * krystal@worthington-biochem.com * Up: Worthington Enzyme Manual Pepsin | | | | | |
E.C. 3.4.23.1
On this page: * Products * Physical Properties * Specificity * Applications * Inhibitors * Substrates * Kinetics, Solubility and Solution Stability * References
Physical Properties
Pepsin, a member of the Peptidase A1 family, is the predominant digestive protease in the gastric juice of vertebrates.
Molecular Weight: 34,620 (from porcine amino acid sequence)1 pI: 2.2 - 3.02; 2.2, 2.83 (porcine) λmax: 278 nm4 Extinction coefficient: EmM = 51.34 (porcine)

Specificity
Pepsin, unlike some other endopeptidases, hydrolyzes only peptide bonds. It does not hydrolyze non-peptide amide or ester linkages.
Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions. Increased susceptibility to hydrolysis occurs if there is a sulfur-containing amino acid close to the peptide bond, which has an aromatic amino acid.
Cleaves Phe1Val, Gln4His, Glu13Ala, Ala14Leu, Leu15Tyr, Tyr16Leu, Gly23Phe, Phe24Phe and Phe25Tyr bonds in the B chain of insulin.5
Pepsin will also preferentially cleave at the carboxyl side of phenylalanine and leucine and to a lesser extent at the carboxyl side of glutamic acid residues. Pepsin will not cleave at valine, alanine, or glycine linkages.6 Amidation of the C-terminal carboxyl group prevents hydrolysis by pepsin.6,7 back to top
Applications
Pepsin is commonly used in the preparation of F(ab')2 fragments from antibodies. In some assays it is preferable to use only the antigen binding (Fab) portion of the antibody. For these applications, antibodies may be enzymatically digested to produce either an Fab or an F(ab')2 fragment of the antibody. To produce an F(ab')2 fragment, IgG is digested with pepsin, which cleaves the heavy chains near the hinge region. One or more of the disulfide bonds that join the heavy chains in the hinge region are preserved, so the two Fab regions of the antibody remain joined together, yielding a divalent molecule (containing two antibody binding sites), hence the designation F(ab')2. The light chains remain intact and attached to the heavy chain. The Fc fragment is digested into small peptides. Fab fragments are generated by cleavage of IgG with papain instead of pepsin. Papain cleaves IgG above the hinge region containing the disulfide bonds that join the heavy chains, but below the site of the disulfide bond between the light chain and heavy chain. This generates two separate monovalent (containing a single antibody binding site) Fab fragments and an intact Fc fragment. The fragments can be purified by gel filtration, ion exchange, or affinity chromatography. Protocols for antibody digestion and purification of antibody fragments can be found in Antibodies: A Laboratory Manual, E. Harlow and D. Lane, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988 (A2926).
Fab and F(ab')2 antibody fragments are used in assay systems where the presence of the Fc region may cause problems. In tissues such as lymph nodes or spleen, or in peripheral blood preparations, cells with Fc receptors (macrophages, monocytes, B lymphocytes, and natural killer cells) are present which can bind the Fc region of intact antibodies, causing background staining in areas that do not contain the target antigen. Use of F(ab')2 or Fab fragments ensures that the antibodies are binding to the antigen and not Fc receptors. These fragments may also be desirable for staining cell preparations in the presence of plasma, because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow more exact localization of the target antigen, i.e. in staining tissue for electron microscopy. The divalency of the F(ab')2 fragment enables it to cross-link antigens, allowing use for precipitation assays, cellular aggregation via surface antigens, or rosetting assays. The optimal pH for the pepsin reaction is 1.5-2.5, which will not be detrimental to the antibody, if it is not exposed for long durations to the low pH. Solutions should be adjusted to neutral pH for storage. The control of pepsin digestion of antibodies has been reported.8

For general digestion of proteins, suggested conditions are a 0.4% solution of pepsin in 10 mM HCl, and digestion for 30-90 minutes at 37 °C. Pepsin has optimal activity with native proteins at approximately pH 1.0, but with some denatured proteins the optimal activity is at approximately pH 1.5-3.5.9,10 back to top Inhibitors | Product No. | Product Name | Add to
Cart | P5318 | Pepstatin A microbial, ≥90% (HPLC) | | P7424 | Pepsinostreptin ≥97% (HPLC) | | P7626 | Phenylmethanesulfonyl fluoride ≥98.5% (GC) | | Substrates | Product No. | Product Name | Add to
Cart | H2625 | Hemoglobin from bovine blood suitable for protease substrate, substrate powder | | F5255 | Fibrin Blue suitable for substrate for pepsin at low pH (High blanks result at high pH) | | 96150 | Z-Glu-Tyr BioChemika, substrate for the det. of pepsin, ≥99.0% (HPLC) | | 77431 | Phe-Ala-Ala-Phe(4-NO2)-Phe-Val-Leu (4-pyridylmethyl) ester BioChemika, ≥98.0% (TLC) | | back to top
Kinetics, Solubility and Solution Stability
Pepsin is soluble in deionized water at 1% (10 mg/ml) and at 0.4% (4 mg/ml) in cold 10 mM hydrochloric acid. Solutions at pH 4.4 are stable at -20 °C for about 2-3 months.12 The pH optimum for activity for porcine pepsin is ~2.2. At pH 1.5 pepsin exhibits about 90% of maximum activity, and at pH 4.5 about 35% of maximum activity.13 Solutions are stable at pH 6-7. Bringing the pH up to 8; however, will irreversibly inactivate pepsin. Pepsin is irreversibly denatured at pH 8.5 - 11 at room temperature.14

Products | Product No. | Product Name | Add to
Cart | P7000 | Pepsin from porcine gastric mucosa, powder, ≥250 units/mg solid | | P6887 | Pepsin from porcine gastric mucosa lyophilized powder, 3,200-4,500 units/mg protein | | P7012 | Pepsin from porcine gastric mucosa, lyophilized powder, ≥2,500 units/mg protein | | P7125 | Pepsin from porcine gastric mucosa, powder, ≥400 units/mg protein | | P0609 | Pepsin−Agarose from porcine gastric mucosa lyophilized powder, 30-70 units/mg dry solid | | P1490 | Pepsinogen I human | | P4656 | Pepsinogen from porcine stomach Grade I-S, lyophilized powder, ~3,000 units/mg protein (after activation to pepsin at pH 2.0 at 25°C) | |
References
1. Sepulveda. P., et al., Primary Structure of Porcine Pepsin. III. Amino Acid Sequence of a Cyanogen Bromide Fragment, CB2A, and the Complete Structure of Porcine Pepsin. J. Biol. Chem., 250, 5082 (1975). 2. Jonsson, M., Isoelectric Spectra of Native and Base Denatured Crystallized Swine Pepsin. Acta Chem. Scand., 26, 3435-3440 (1972). 3. Malamud, D., and Drysdale, J.W., Isoelectric Points of Proteins: A Table, Anal. Biochem., 86, 620-647 (1978). 4. Proc. Natl. Acad. Sci., 45, 915-922 (1959). 5. IUBMB Enzyme Nomenclature: http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/1.html 6. Sweeney, P.J., and Walker, J.M., in Enzymes of Molecular Biology, Burrell, M.M., ed., Humana Press (Totowa, NJ: 1993), pp. 290-291. 7. Enzymes, Dixon, M., et al., Academic Press (New York, NY: 1979), p. 262. 8. Rea, D.W., and Ultee, M.E., A Novel Method for Controlling the Pepsin Digestion of Antibodies. J. Immunol. Meth., 157, 165-173 (1993). 9. Arch. Biochem. Biophys., 57, 163-173 (1955). 10. J. Biol. Chem., 234, 3137-3145 (1959). 11. Knowles, J.R., et al., The pH-dependence of the Binding of Competitive Inhibitors to Pepsin. Biochem. J., 113, 343-51 (1969). 12. Rajagopalan, T.G., et al., Pepsin from Pepsinogen. Preparation and Properties. J. Biol. Chem., 241, 4940 (1966). 13. Bohak, Z.; J. Biol. Chem,. 244, 4638-4648 (1969) 14. Ryle, A.P., The Porcine Pepsins and Pepsinogens. Methods in Enzymol., 19, 316-336 (1970).
Description
Analysis Note
E1%/280=14.7
Optimum pH is 2-4. Active in 4 M urea and 3 M guanidine HCl. Stable at 60 °C. Pepsin is irreversibly inactivated at pH 8.0 - 8.5.
Protein determined by E1%/280
Application
Used to produce F(ab′)2 fragments of antibodies.
Pepsin is a peptidase used to digest proteins and is commonly used in the preparation of Fab fragments from antibodies. Pepsin, from porcine gastric mucosa, has been used to hydrolyze dry cervical samples in mice1.
Other Notes
View more information on pepsin at www.sigma-aldrich.com/enzymeexplorer.
Unit Definition
One unit will produce a ΔA280 of 0.001 per min at pH 2.0 at 37°C, measured as TCA-soluble products using hemoglobin as substrate. (Final volume = 16mL. Light path = 1cm.)
Biochem/physiol Actions
Pepsin hydrolyzes peptide bonds, not amide or ester linkages. Pepsin cleaves peptides with an aromatic acid on either side of the peptide bond. Sulfur-containing amino acids increase susceptibility to hydrolysis when they are close to the peptide bond. Pepsin preferentially cleaves at the carboxyl side of phenylalanine and leucine and at the carboxyl side of glutamic acid residues. Cleaves Phe-Val, Gln-His, Glu-Ala, Ala-Leu, Leu-Tyr, Tyr-Leu, Gly-Phe, Phe-Phe and Phe-Tyr bonds in the β chain of insulin
Pepsin is the major proteolytic enzyme produced in the stomach. It digests proteins through the cleavage of interior peptide linkages.2
Preferential cleavage: hydrophobic and aromatic residues in P1 and P1′ postitions. Cleaves Phe-Val, Gln-His, Glu-Ala, Ala-Leu, Leu-Tyr, Tyr-Leu, Gly-Phe, Phe-Phe and Phe-Tyr bonds in the β chain of insulin

Pepsin is the major proteolytic enzyme produced in the stomach. It digests proteins through the cleavage of interior peptide linkages.2 * What is pepsin?
The enzyme named pepsin is released by some chief cells that can be found in the stomach. This enzyme has the capability and the role of degrading food proteins into peptides, thus producing digestion. Discovered in 1836, pepsin was the first revealed enzyme and also the first that was crystallized. Being a digestive protease, the substance is among three main ones that help humans in the digestion process. It works by breaking down dietary proteins and separating them into different components in order for these to be easily absorbed by the intestinal lining. It has a significant role when it comes to human’s digestion process which couldn’t be complete without the existence of it.
The digestive enzyme is in fact produced by the precursor substance called pepsiongen that is in the lining of the stomach cells. Pepsin is also produced within these cells, being excreted as a response to the food that enters the digestive tract. Inside the human body pepsin can appear in more than one form, but the most important and active one is pepsin A. Being the main component among all stomach’s juices, this enzyme has many health benefits that makes the human body function properly.
The uses of pepsin are mainly connected to preparing antibodies. The enzyme has a major role in their production, as it helps digest the IgG, which is a substance that cleaves all heavy chains close to the hinge region. Besides this, pepsin is also used in the preparation of collagen for cosmetic purposes. It can additionally be inhibited in 2 different ways. The very first method introduces an inhibitor compound from the pepsin enzyme and the second is to decrease the level of acidity and thus, the enzyme becomes inactive. The process occurs when the pH usually reaches a level of 4 to 5. Regarding the primary benefits of pepsin, scientists have managed to uncover that it can: * Digest proteins and breaks them into pieces * Stimulate bile secretion * Absorb vitamin B12
The supplements and drugs available are over the counter pills and can be taken without medical prescription. Several supplements might or might not have HCI within the capsule. Physicians believe that boosted HCI together with pepsin could help digestion and absorb vitamins and minerals faster. * Health benefits
When it comes to health benefits, pepsin can come in handy, as it can be used for a wide variety of health problems, such as: * Dyspepsia * vomiting caused by morning sickness during pregnancy * gastralgia * apepsia of infants * obstinate vomiting * diarrhea * cancer treatments
As there aren’t any known side effects caused by the usage of this enzyme in the treatment of different ailments, it can be incorporated with confidence in the healing of conditions enumerated above. Nonetheless, a medical specialist has to be always consulted and the treatment with pepsin supplements has to be conducted under medical supervision.
If the body doesn’t produce the appropriate amount of pepsin, supplements are highly recommended. As pepsin helps digestion, it’s directly responsible for keeping the human body toxin-free and stimulating the liver to produce bile that leads to the elimination of toxins. Within the stomach, pepsin doesn’t work all the way through in digesting the proteins that enter the body in amino acids. The process of breaking down amino acids is conducted in the small intestine, where pepsin also plays a great role. Being the major element in two main parts of the body and the key factor that prevents the organism from getting intoxicated, this enzyme can’t miss from the organism. * Medical benefits
In what concerns the medical benefits of pepsin, there have been very clear results. All conducted studies have shown that pepsin is the main digestive for all proteins that are part of the human diet. The dietary proteins have the form of large molecules that are very difficult to absorb. In order to be properly absorbed by the human body, they have to be broken down into polypeptides, which are smaller particles of the molecules ingested in the first place. According to the UC Clermont College, pepsin is the main enzyme in the body that can do that, thus providing digestion. In the absence of it, the human body would be seriously inhibited when it came to the ability of metabolizing proteins.
As said by the National Digestive Diseases Information Clearinghouse, pepsin is also responsible for stimulating the liver and the gallbladder. Once this enzyme is released in the body, all the receptors that tell the liver and the gallbladder to secrete bile in the small intestines, activate. As bile is essential in the digestive process and couldn’t exist without pepsin, it makes the latter vital for the proper functioning of the human body.
Moreover, according to the American Journal of Clinical Nutrition, pepsin is also responsible for the absorption of vitamin B12 in the body. This vitamin is essential for human beings, the absence of it leading to serious health issues. In order for this vitamin to be properly absorbed, pepsin has to be among the substances from the gastric acids which make the digestion possible.
One of the most interesting and surprising benefits that pepsin offers to the body are the dental ones. According to the book entitled ‘Dental Medicine: A Manual of Dental Materia Medica and Therapeutics’, written by Ferdinand Gorgas, pepsin can also be effectively when used for infected or putrid teeth, as it has antiseptic qualities. It can be applied directly on the affected areas of the teeth, but it has to be used in very small amounts, as it has strong hydrochloric properties that could cause more harm.
Another study conducted by the University of Maryland Medical Center, has demonstrated that pepsin is a critically important enzyme that balances and regulates human’s digestion in both the stomach and the intestines. But besides improving the digestion process, pepsin also produces a negative reaction in the body, as it’s responsible for causing digestive ulcers in case it is found in high quantities in the body. Thus, the enzyme cannot be merged with treatments recommended for gastric ulcers, as it may aggravate the patient’s state.
Introduction
Pepsin terms a small group of gastric proteases that are active in acidic environments with a pH between 1 and 5. Its name comes from the Greek word pepsis, which means to digest. The most studied and commercially available form of pepsin is porcine pepsin A, isolated from the gastric mucosa of a pig. Pepsin is not directly formed after translation of its coding mRNA, but instead begins as a zymogen, or an inactive precursor. This preliminary, inactive form that is initially translated is called pepsinogen. The activation of pepsinogen is accomplished by lowering the pH below 4.5, which leads to a cascade of changes in bond structure, as shown in Figure 2 below, and yields the enzyme pepsin. The first step is reversable, however once the protein has progressed beyond step II, the protein cannot revert back to the inactive pepsinogen. (James and Sielecki, 1986)

Figure 2. Proposed steps in the activation of pepsinogen into pepsin. Note that pepsin ends up with 44 amino acids less than pepsinogen, left out of the final enzyme after step IV.
Source: James and Sielecki, 1986

Structure

Figure 3. Amino acid sequence and overall makeup of porcine pepsin A
Source: Tang, et al. 1973 Porcine Pepsin A has a molecular weight of 36,000 Da and is made up of 327 amino acids. The protein is made up of two domains with intracellular symmetry, as observed in other aspartyl proteases. It has been proposed by that this structure is due to a duplication of a gene corresponding to a pair of identical precursor proteins that fused to form the pepsin we find today. Support for this theory has come from the finding that the aspartic proteinases of the human immunodeficiency virus (HIV-1) and the Rous sarcoma virus (RSV) are dimeric proteins in which two separate subunits correspond to the lobes of pepsin. (Pearl and Taylor, 1987) Pepsinogen, the inactive protein that transforms to pepsin at low pH, has an additional 44 amino acids on its N-terminus that are released during the transformation. All aspartyl proteases belong to the class of "β-proteins". As the name reveals, pepsin is made up mostly of β-sheets with only 6 observed helical sections, none consisting of more than 10 amino acids. Pepsin has fewer basic amino acid residues than any other proteins as shown in figure 3: 1 lysine, 2 arginines, and 1 histidine. In contrast, the enzyme has 44 acidic residues. This helps explain pepsin's stability at extremely low pH because positive charges in acid media decrease the stability of polymeric structures. The complex tertiary hydrogen bonding of the molecule between the β sheets and other elements further contributes to the structure's acidic stability. Pepsin also has 3 disulfide bridges. Pepsin, as depicted in figures 1 and 4, has a crescent moon shape with a large, obvious active site. This site is inhibited in Figure 1 by the potent protease inhibitor pepstatin. (Andreeva, et al. 1893)

Figure 4. These three images model the tertiary structure of porcine pepsin A. The leftmost image, labeled a, depicts the intradomain double-layer mixed β-sheet that can be found in each of the two domains. The center image, labeled b, depicts the interdomain section mostly consisting of β-sheets. These two elements together can be seen in the third image making up the protein as a whole. The elements from two domains with the complex double-layer structure can be seen on either side of the interdomain section.
Source: Andreeva et al. 1983

Function Pepsin is an enzyme which breaks down polypeptides through a general acid-base catalysis in which water is an essential participant. This process involves the abstraction of a protein from water, so the low pH atmosphere plays a central role in the enzyme's function. The pH causes the denaturation of most proteins, ensuring the tertiary structure of these polypeptides does not prevent the active site of pepsin from breaking them down. Porcine pepsin A is found in the gut of pigs and a very similar pepsin is also present in the human gut. This pepsin is released by the gut following the ingestion of food by the organism so that the proteins in the food can be broken down and eventually turned into energy. The signal pathway is begun by the vagus nerve and leads to the release of both gastric acid, also known as hydrochloric acid, and pepsinogen. The hydrochloric acid lowers the pH, triggering the conversion of inactive pepsinogen into active pepsin and facilitating the breakdown of any polypeptides in the ingested food. (Fruton, 2002)

Figure 5. Stereogram showing the overall structure of human pepsin from both sides. Main-chain atoms are shown with the associated hydrogen bonds shown with broken lines. Note that this is an image of human pepsina nd may differ slightly from the previous Figures of porcine pepsin A.
Source: Fujinaga et al. 1995

Works Cited
1. James M, Sielecki A. Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Angstrom resolution. Nature. 1986; 319: 33-38
2. Tang J, Sepulveda P, Jarciniszyn, Jr J, Chen K, Huang W-Y, Tao N, Liu D, Lanier J. Amino-Acid Sequence of Porcine Pepsin. Proc Nat Acad Sci 1973; 70, 12, I: 3437-3439.
3. Pearl L, Taylor W. A structural model for the retroviral proteases. Nature 1987; 329: 351-354.
4. Andreeva N, Zdanov A, Gustchina A, Fedorov A. Structure of Ethanol-inhibited Porcine Pepsin at 2-Angstrom Resolution and Binding of the Methyl Ester of Phenylanyl-diiodotyrosine to the Enzyme. Journal of Biological Chemistry 1983; 259, 18: 11353-11365.
5. Fruton J. A History of Pepsin and Related Enzymes. The Quarterly Review of Biology. 2002; 77, 2: 127-143.
6. Fujinaga M, Chernaia M, Tarasova N, Mosimann S, James M. Crystal Structure of human pepsin and its complex with pepstatin. Protein Science,1995; 4: 960-972.