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definition - Casomorphin

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  Bovine β-casomorphin 7, a casomorphin, has seven amino acids in its peptide sequence.

Casomorphins are peptides, i.e., protein fragments, derived from the digestion of milk protein casein. The distinguishing characteristic of casomorphins is that they have an opioid effect.[1]

The most important casomorphins from bovine milk are those released from the digestion of β-casein into β-casomorphins, sometimes denoted as BCM followed by a numeral indicating the number of amino acids in the sequence. In cattle, the amount of β-casein - and, hence, the potential release of β-casomorphins - varies between species and breeds. Typically, β-casein comprises about one-third of the casein in milk, or about 12 grams per liter of milk. However, there are at least 13 different variants of the β-casein protein in cattle population, with any one cow producing milk that will contain either one or two of these 13 variants. β-casomorphins are found in cheeses made from bovine milk; their concentrations are higher in mould cheeses (e.g. Brie, Rokpol) than in semi-hard cheeses (e.g. Edam, Gouda and Kasztelan).[1]

Each variant fits into one of two main categories known as A1 and A2. In cattle, A1-type β-caseins have the amino acid histidine at position 67, whereas the A2-type β-caseins have the amino acid proline at position 67. Laboratory experiments show that the casomorphin known as BCM7 is released only from the A1-type β-caseins.[2] The potential release of BCM7 is about 0.4 grams per litre of milk (assuming as above that there are 12g of β-casein per litre).

Human digestion may break down casomorphins into inactive dipeptides by the enzyme dipeptidyl peptidase-4.[3][4] This enzyme is found in the digestive tract and in some endocrine cells.

There is also the potential for release of casomorphins from human milk. However, human BCM7 (Tyr-Pro-Phe-Val-Glu-Pro-Ile) differs from the bovine form (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) at two amino acid positions.[citation needed]

Scientific understanding of the biochemistry and pharmacology of casomorphins is incomplete. A recent scientific review is provided by Kaminski et al. (2007).[5]



Casein has been documented to break down in the stomach to produce the peptide casomorphin, an opioid that acts as a histamine releaser.[6]

Diets that eliminate foods containing casein are promoted at conferences for parents of children with ASD, and some books, web sites, and discussion groups contain testimonials describing benefits in autism-related symptoms, notably social engagement and verbal skills.[7] Studies supporting these claims have had significant flaws, so the data is inadequate to guide treatment recommendations.[7] These ideas were tested using sensitive and specific assays based on a combination of HPLC and mass spectrometry, but these peptides cannot be detected in autistic children's urine.[8][9] The previous reports of these peptides used less specific assays and were strongly criticised as using unreliable methods that were prone to false positive results.[10] However, proponents continue to argue that these peptides are implicated in a number of medical conditions, including diabetes, heart disease, and symptoms of autism and schizophrenia.[11]

  Some known casomorphins

  β-Casomorphin 1-3

  • Structure: H-Tyr-Pro-Phe-OH
  • Chemical formula: C23H27N3O5
  • Molecular weight: 425.48 g/mol

  Bovine β-casomorphin 1-4

  • Structure: H-Tyr-Pro-Phe-Pro-OH
  • Chemical formula:
  • Molecular weight: 522.61 g/mol

  Bovine β-casomorphin 1-4, amide

  • Structure: H-Tyr-Pro-Phe-Pro-NH2
  • Chemical formula: C28H35N5O5
  • Molecular weight: 521.6 g/mol

Also known as morphiceptin

  Bovine β-casomorphin 5

  • Structure: H-Tyr-Pro-Phe-Pro-Gly-OH
  • Chemical formula: C30H37N5O7
  • Molecular weight: 594.66 g/mol

  Bovine β-casomorphin 7

  • Structure: H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-OH
  • Chemical formula: C41H55N7O9
  • Molecular weight: 789.9 g/mol

  Bovine β-casomorphin 8

  • Structure: H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-OH
  • Chemical formula: C46H62N8O10
  • Molecular weight: 887.00 g/mol

(Note: There is also a form of bovine β-Casomorphin 8 that has histidine instead of proline in position 8, depending on whether it is derived from A1 or A2 beta-casein.)


  1. ^ a b http://www.sciencedirect.com/science/article/pii/S0958694608001970
  2. ^ Jinsmaa Y, Yoshikawa M, 1999; "Enzymatic release of neocasomorphin and beta-casomorphinfrom bovine beta-casein"; Peptides 20:957-962
  3. ^ Püschel G, Mentlein R, Heymann E (1982). "Isolation and characterization of dipeptidyl peptidase IV from human placenta". Eur J Biochem 126 (2): 359–365. DOI:10.1111/j.1432-1033.1982.tb06788.x. PMID 6751824. 
  4. ^ Converse PJ, Hamosh A, McKusick VA (2005). DIPEPTIDYL PEPTIDASE IV; DPP4. Online Mendelian Inheritance in Man.
  5. ^ Stanislaw Kaminski, Anna Cielinska, Elzbieta Kostyra (2007). "Polymorphism of bovine beta-casein and its potential effect on health". Journal of Applied Genetics 48 (3): 189–198. DOI:10.1007/BF03195213. PMID 17666771. 
  6. ^ Kurek M, Przybilla B, Hermann K, Ring J (1992). "A naturally occurring opioid peptide from cow's milk, beta-casomorphine-7, is a direct histamine releaser in man". Int Arch Allergy Immunol 97 (2): 115–120. DOI:10.1159/000063326. PMID 1374738. 
  7. ^ a b Christison GW, Ivany K (2006). "Elimination diets in autism spectrum disorders: any wheat amidst the chaff?". J Dev Behav Pediatr 27 (2 Suppl 2): S162–71. DOI:10.1097/00004703-200604002-00015. PMID 16685183. 
  8. ^ Dettmer K, Hanna D, Whetstone P, Hansen R, Hammock BD (August 2007). "Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory". Anal Bioanal Chem 388 (8): 1643–51. DOI:10.1007/s00216-007-1301-4. PMID 17520243. 
  9. ^ Cass H, Gringras P, March J, et al. (September 2008). "Absence of urinary opioid peptides in children with autism". Arch. Dis. Child. 93 (9): 745–50. DOI:10.1136/adc.2006.114389. PMID 18337276. 
  10. ^ Hunter LC, O'Hare A, Herron WJ, Fisher LA, Jones GE (February 2003). "Opioid peptides and dipeptidyl peptidase in autism". Dev Med Child Neurol 45 (2): 121–8. DOI:10.1111/j.1469-8749.2003.tb00915.x. PMID 12578238. 
  11. ^ http://aut.sagepub.com/cgi/content/abstract/3/1/85

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