Erepsin

Last updated

Erepsin is a mixture of enzymes contained in a protein fraction found in the intestinal juices that digest peptones into amino acids. It is produced and secreted by the intestinal glands in the ileum and the pancreas, but it is also found widely in other cells. However, the term now rarely used in scientific literature as more precise terms are preferred.

Contents

History

Erepsin was discovered at the beginning of the twentieth century by German physiologist Otto Cohnheim (1873-1953) who found a substance that breaks down peptones into amino acid in the intestines. [1] [2] He termed this hypothetical protease in his protein extract "erepsin" in 1901, derived from a Greek word meaning "I break down" (έρείπω). [3] His discovery was significant as it overturned the previous "hypothesis of resynthesis" which proposed that proteins get broken down into peptones from which proteins may then be resynthesized, and helped establish the idea of free amino acids instead of peptones being the building blocks of protein. [3]

Erepsin was originally thought to be a single enzyme or a mixture of a few enzymes involved in the terminal stages of the breakdown of peptides to free amino acids in the intestines. [4] However, it became clear later that erepsin is in fact a complex mixture of different peptidases. [5] It was also found not to be unique to intestinal mucosa and is present widely in many other cells and organisms. [6] [7] [8] The term erepsin fell from use in scientific literature in the latter half of the twentieth century as scientists considered its use as a term for a single enzyme or a few enzymes misleading, [9] and more precise terms such as aminopeptidase, carboxypeptidase and dipeptidase are preferred. The term is now considered obsolete. [10]

Properties

Erepsin may contain dipeptidases, aminopeptidases, occasionally carboxypeptidases, and these include leucyl aminopeptidase, prolinase, prolidase and others. [5] It is often grouped under exopeptidases, proteases that work only on the outermost peptide bonds of a polypeptide chain. The optimum pH for the group of enzymes is around pH 8, but some individual enzymes within this group may be distinguished by their differences in stability and optimum pH. [5]

Related Research Articles

<span class="mw-page-title-main">Proteolysis</span> Breakdown of proteins into smaller polypeptides or amino acids

Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion.

<span class="mw-page-title-main">Trypsin</span> Family of digestive enzymes

Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the digestive system of many vertebrates, where it hydrolyzes proteins. Trypsin is formed in the small intestine when its proenzyme form, the trypsinogen produced by the pancreas, is activated. Trypsin cuts peptide chains mainly at the carboxyl side of the amino acids lysine or arginine. It is used for numerous biotechnological processes. The process is commonly referred to as trypsinogen proteolysis or trypsinization, and proteins that have been digested/treated with trypsin are said to have been trypsinized.

<span class="mw-page-title-main">Protease</span> Enzyme that cleaves other proteins into smaller peptides

A protease is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in numerous biological pathways, including digestion of ingested proteins, protein catabolism, and cell signaling.

<span class="mw-page-title-main">Digestive enzyme</span> Class of enzymes

Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.

<span class="mw-page-title-main">Alanine aminopeptidase</span> Mammalian protein found in Homo sapiens

Membrane alanyl aminopeptidase also known as alanyl aminopeptidase (AAP) or aminopeptidase N (AP-N) is an enzyme that in humans is encoded by the ANPEP gene.

An exopeptidase is any peptidase that catalyzes the cleavage of the terminal peptide bond; the process releases a single amino acid, dipeptide or a tripeptide from the peptide chain. Depending on whether the amino acid is released from the amino or the carboxy terminal, an exopeptidase is further classified as an aminopeptidase or a carboxypeptidase, respectively. Thus, an aminopeptidase, an enzyme in the brush border of the small intestine, will cleave a single amino acid from the amino terminal, whereas carboxypeptidase, which is a digestive enzyme present in pancreatic juice, will cleave a single amino acid from the carboxylic end of the peptide.

<span class="mw-page-title-main">Cysteine protease</span> Class of enzymes

Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.

<span class="mw-page-title-main">Carboxypeptidase</span> Class of enzymes

A carboxypeptidase is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. This is in contrast to an aminopeptidases, which cleave peptide bonds at the N-terminus of proteins. Humans, animals, bacteria and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation. At least two mechanisms have been discussed.

<span class="mw-page-title-main">Dipeptidyl peptidase-4</span> Mammalian protein found in humans

Dipeptidyl peptidase-4, also known as adenosine deaminase complexing protein 2 or CD26 is a protein that, in humans, is encoded by the DPP4 gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner, and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].

Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems.

<span class="mw-page-title-main">Aminopeptidase</span> Class of enzymes

Aminopeptidases are enzymes that catalyze the cleavage of amino acids from the N-terminus (beginning), of proteins or peptides. They are found in many organisms; in the cell, they are found in many organelles, in the cytosol, and as membrane proteins. Aminopeptidases are used in essential cellular functions, and are often zinc metalloenzymes, containing a zinc cofactor.

Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.

<span class="mw-page-title-main">Cathepsin D</span> Protein-coding gene in the species Homo sapiens

Cathepsin D is a protein that in humans is encoded by the CTSD gene. This gene encodes a lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes. The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal compartments. This proteinase, which is a member of the peptidase A1 family, has a specificity similar to but narrower than that of pepsin A. Transcription of the CTSD gene is initiated from several sites, including one that is a start site for an estrogen-regulated transcript. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. Homozygous deletion of the CTSD gene leads to early lethality in the postnatal phase. Deficiency of CTSD gene has been reported an underlying cause of neuronal ceroid lipofuscinosis (NCL).

<span class="mw-page-title-main">CPM (gene)</span> Protein-coding gene in humans

Carboxypeptidase M is an enzyme that in humans is encoded by the CPM gene.

<span class="mw-page-title-main">DPP7</span> Protein-coding gene in the species Homo sapiens

Dipeptidyl-peptidase 2 is an enzyme that in humans is encoded by the DPP7 gene.

<span class="mw-page-title-main">CPA3</span> Enzyme found in humans

Carboxypeptidase A3 (mast cell carboxypeptidase A), also known as CPA3, is an enzyme which in humans is encoded by the CPA3 gene. The "CPA3" gene expression has only been detected in mast cells and mast-cell-like lines, and CPA3 is located in secretory granules. CPA3 is one of 8-9 members of the A/B subfamily that includes the well-studied pancreatic enzymes carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and carboxypeptidase B. This subfamily includes 6 carboxypeptidase A-like enzymes, numbered 1-6. The enzyme now called CPA3 was originally named mast cell carboxypeptidase A, and another protein was initially called CPA3. A gene nomenclature committee renamed mast cell carboxypeptidase A as CPA3, and the original CPA3 reported by Huang et al. became CPA4 to reflect the order of their discovery.

<span class="mw-page-title-main">Aminopeptidase Y</span> Class of enzymes

Aminopeptidase Y is an enzyme. This enzyme catalyses the following chemical reaction

Methionyl aminopeptidase is an enzyme. This enzyme catalyses the following chemical reaction

Dipeptidyl-peptidase II is an enzyme. This enzyme catalyses the following chemical reaction:

<span class="mw-page-title-main">Peptidyl-dipeptidase Dcp</span> Class of enzymes

Peptidyl-dipeptidase Dcp (EC 3.4.15.5, dipeptidyl carboxypeptidase (Dcp), dipeptidyl carboxypeptidase) is a metalloenzyme found in the cytoplasm of bacterium E. Coli responsible for the C-terminal cleavage of a variety of dipeptides and unprotected larger peptide chains. The enzyme does not hydrolyze bonds in which P1' is Proline, or both P1 and P1' are Glycine. Dcp consists of 680 amino acid residues that form into a single active monomer which aids in the intracellular degradation of peptides. Dcp coordinates to divalent zinc which sits in the pocket of the active site and is composed of four subsites: S1’, S1, S2, and S3, each subsite attracts certain amino acids at a specific position on the substrate enhancing the selectivity of the enzyme. The four subsites detect and bind different amino acid types on the substrate peptide in the P1 and P2 positions. Some metallic divalent cations such as Ni+2, Cu+2, and Zn+2 inhibit the function of the enzyme around 90%, whereas other cations such as Mn+2, Ca+2, Mg+2, and Co+2 have slight catalyzing properties, and increase the function by around 20%. Basic amino acids such as Arginine bind preferably at the S1 site, the S2 site sits deeper in the enzyme therefore is restricted to bind hydrophobic amino acids with phenylalanine in the P2 position. Dcp is divided into two subdomains (I, and II), which are the two sides of the clam shell-like structure and has a deep inner cavity where a pair of histidine residues bind to the catalytic zinc ion in the active site. Peptidyl-Dipeptidase Dcp is classified like Angiotensin-I converting enzyme (ACE) which is also a carboxypeptidase involved in blood pressure regulation, but due to structural differences and peptidase activity between these two enzymes they had to be examined separately. ACE has endopeptidase activity, whereas Dcp strictly has exopeptidase activity based on its cytoplasmic location and therefore their mechanisms of action are differentiated. Another difference between these enzymes is that the activity of Peptidyl-Dipeptidase Dcp is not enhanced in the presence of chloride anions, whereas chloride enhances ACE activity.

References

  1. ↑ Joseph S. Fruton (1990). Contrasts in Scientific Style: Research Groups in the Chemical and Biochemical Sciences. Vol. 191. American Philosophical Society. pp. 105–106. ISBN   0-87169-191-4.
  2. ↑ Cohnheim, 0 (1901). "Die Umwandlung des Eiweis s durch die Darmwand". Zeitschrift für Physiologische Chemie. 33 (5–6): 451–465. doi:10.1515/bchm2.1901.33.5-6.451.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  3. 1 2 Matthews DM (1978). "Otto Cohnheim--the forgotten physiologist". British Medical Journal. 2 (6137): 618–9. doi:10.1136/bmj.2.6137.618. PMC   1607550 . PMID   359089.
  4. ↑ Emil L Smith (1948). "The peptidases of skeletal, heart and uterine muscle". Journal of Biological Chemistry. 173 (2): 553–569. doi: 10.1016/S0021-9258(18)57428-7 . PMID   18910712.
  5. 1 2 3 Emil L Smith; Max Bergmann (1944). "The peptidases of intestinal mucosa" (PDF). Journal of Biological Chemistry. 153 (2): 627–651. doi: 10.1016/S0021-9258(18)72006-1 .
  6. ↑ H. M. Vernon (1904). "The universal presence of erepsin in animal tissues". J Physiol. 32 (1): 33–50. doi:10.1113/jphysiol.1904.sp001063. PMC   1465616 . PMID   16992755.
  7. ↑ Nathan Berman & Leo F. Rettger (1916). "Bacterial Nutrition: a Brief Note on the Production of Erepsin by Bacteria". Journal of Bacteriology. 1 (5): 537–539. doi:10.1128/jb.1.5.537-539.1916. PMC   378674 . PMID   16558717.
  8. ↑ HS Reed and HS Stahl (1911). "The Erepsins of Glomerella Rufomaculans and Sphaeropsis Malorum" (PDF). Journal of Biological Chemistry. 10 (2): 109–112. doi: 10.1016/S0021-9258(18)91427-4 .
  9. ↑ Emil L Smith (1949). James Murray Luck (ed.). "Proteolytic enzymes". Annual Review of Biochemistry. 18: 35. doi:10.1146/annurev.bi.18.070149.000343.
  10. ↑ James Batcheller Sumner; George Frederick Somers (1943). Chemistry and methods of enzymes. Academic Press. p. 146.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.