Casomorphin
Encyclopedia
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.
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. Edamski, Gouda
and Kasztelan) .
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. 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
. 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.
Scientific understanding of the biochemistry and pharmacology of casomorphins is incomplete. A recent scientific review is provided by Kaminski et al. (2007).
has been documented to break down in the stomach to produce the peptide casomorphin, an opioid
that acts as a histamine
releaser.
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. Studies supporting these claims have had significant flaws, so the data is inadequate to guide treatment recommendations. 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. 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. 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.
Also known as morphiceptin
(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.)
Casein
Casein is the name for a family of related phosphoprotein proteins . These proteins are commonly found in mammalian milk, making up 80% of the proteins in cow milk and between 60% and 65% of the proteins in human milk....
. The distinguishing characteristic of casomorphins is that they have an opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
effect.
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
Brie
Brie is a historic region of France most famous for its dairy products, especially Brie cheese. It was once divided into two sections ruled by different feudal lords: the western Brie française, corresponding roughly to the modern department of Seine-et-Marne in the Île-de-France region; the...
, Rokpol
Rokpol
Rokpol is a Polish blue cheese similar to Danish blue cheeses. The name derives from Roquefort and suggests that it is Polish Roquefort....
) than in semi-hard cheeses (e.g. Edamski, Gouda
Gouda (cheese)
Gouda is an orange cheese made from cow's milk. The cheese is named after the city of Gouda in the Netherlands, but its name is not protected. However, the European Commission has confirmed that "Gouda Holland" is to be protected...
and Kasztelan) .
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. 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
Dipeptidyl peptidase-4
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.-Function:...
. 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.
Scientific understanding of the biochemistry and pharmacology of casomorphins is incomplete. A recent scientific review is provided by Kaminski et al. (2007).
Health
CaseinCasein
Casein is the name for a family of related phosphoprotein proteins . These proteins are commonly found in mammalian milk, making up 80% of the proteins in cow milk and between 60% and 65% of the proteins in human milk....
has been documented to break down in the stomach to produce the peptide casomorphin, an opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
that acts as a histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
releaser.
Diets that eliminate foods containing casein
Gluten-free, casein-free diet
A gluten-free casein-free diet eliminates dietary intake of the naturally occurring proteins gluten and casein .-Controversial autism diet:...
are promoted at conferences for parents of children with ASD
Autism spectrum
The term "autism spectrum" is often used to describe disorders that are currently classified as pervasive developmental disorders. Pervasive developmental disorders include autism, Asperger syndrome, Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise...
, and some books, web sites, and discussion groups contain testimonials describing benefits in autism-related symptoms, notably social engagement and verbal skills. Studies supporting these claims have had significant flaws, so the data is inadequate to guide treatment recommendations. These ideas were tested using sensitive and specific assays based on a combination of HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
and mass spectrometry
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
, but these peptides cannot be detected in autistic children's urine. 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. 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.
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: C28H39N5O7
- Molecular weight: 557.64 g/mol
Also known as morphiceptin
Morphiceptin
Morphiceptin is a tetrapeptide that is aselective μ-opioid receptor agonist. It is derived from β-casomorphin and has over 1,000 times selectivity for μ- over δ-opioid receptors. When administered intracerebroventricularly, morphiceptin had an analgesic ED50 of 1.7 nmol per animal...
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.)
External links
- Review of the potential health impact of β-casomorphins and related peptides European Food Safety Agency, Scientific Report (2009) 231, 1-107