Exorphin

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Exorphins are exogenous opioid peptides, distinguished from endorphins, or endogenous opioid peptides.

Contents

Exorphins include opioid food peptides like gluten exorphin and microbial opioid peptides and any other opioid peptide foreign to a host that have metabolic efficacy for that host. [1] Exorphins can be converted from plants and animals but also dairy products and certain vegetables like spinach and soy. [2]

Exorphins can be released for many different kinds of proteins and thus can be isolated from various sources such as from plant proteins or from enzymes of the digestive system of animals. The study of exorphins as a bioactive peptide can be a source of discovery for new kinds of food and drugs to treat and prevent diseases associated with the accumulation of exorphins. [3]

Connection and treatment of autism

Effective therapies to manage autism remain scarce. According to the exorphin theory of autism, an increase in the levels of exorphin is linked to symptoms of autism. Based on this concept, experiments have attempted to reduce the symptoms of autism by using large amounts of protease to break down exorphins before they are absorbed. Experiments have also attempted to enhance and utilize enzymes existing in the gut to break down exorphins in a similar fashion, since the production of exorphins within the gut is inevitable. [4]

Connection with schizophrenia

Exorphins can cause various symptoms of schizophrenia if mutation occurs at a few selected loci. Genetic mutation at one of these loci can lead to increased absorption of exorphins via receptor mediated endocytosis. Another possibility from these particular loci is that catabolization of exorphins can be disrupted thus allowing the exorphin to persist in the body. This would lead to exorphins entering the brain capillary, bypassing the blood brain barrier, and inflicting negative repercussion on the brain. This does not mean that exorphin will necessarily cause schizophrenia, as susceptibility to the disease is dependent on an individual's genetic makeup. [5] However, by increasing the probability that exorphins enter the brain, it will also increase the chance of an individual displaying schizophrenic symptoms.

Related Research Articles

<span class="mw-page-title-main">Gluten</span> Group of cereal grain proteins

Gluten is a structural protein naturally found in certain cereal grains. The term "gluten" usually refers to the combination of prolamin and glutelin proteins that naturally occurs in many cereal grains and that can trigger celiac disease. The types of grains that contain gluten include all species of wheat, as well as barley, rye, and some cultivars of oat. Cross hybrids of any of these grains also contain gluten. Gluten makes up 75–85% of the total protein in bread wheat. Baked goods made of bread become fluffy and stretchy because of gluten.

<span class="mw-page-title-main">Tay–Sachs disease</span> Human medical condition

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur later in childhood, adolescence, or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.

<span class="mw-page-title-main">Coeliac disease</span> Autoimmune disorder that results in a reaction to gluten

Coeliac disease or celiac disease is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body, or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as Type 1 diabetes mellitus and Hashimoto's thyroiditis, among others.

A gluten-free casein-free diet, also known as a gluten-free dairy-free diet, is a diet that does not include gluten, and casein. Despite an absence of scientific evidence, there have been advocates for the use of this diet as a treatment for autism and related conditions.

<span class="mw-page-title-main">Histamine</span> Organic compound involved in immune responses

Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in 1910, it has been considered a local hormone (autocoid) because it lacks the classic endocrine glands to secrete it; however, in recent years, histamine has been recognized as a central neurotransmitter. Histamine is involved in the inflammatory response and has a central role as a mediator of itching. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues. It consists of an imidazole ring attached to an ethylamine chain; under physiological conditions, the amino group of the side-chain is protonated.

<span class="mw-page-title-main">Casomorphin</span> Chemical compound

Casomorphin is an opioid peptide derived from the digestion of the milk protein casein.

<span class="mw-page-title-main">Pleiotropy</span> Influence of a single gene on multiple phenotypic traits

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function.

Gluten exorphins are a group of opioid peptides formed during the digestion of the gluten protein. These peptides work as external regulators for gastrointestinal movement and hormonal release. The breakdown of gliadin, a polymer of wheat proteins, creates amino acids that stop the gluten epitopes from entering the immune system to activate inflammatory reactions. During this process, gluten does not fully break down, thus increasing the presence of gluten exorphins. Because of this, researchers think this is what might lead to various diseases.

The rubiscolins are a group of opioid peptides that are formed during digestion of the ribulose bisphosphate carboxylase/oxygenase (Rubisco) protein from spinach leaves. These peptides have much in common with the better-known gluten exorphins.

<span class="mw-page-title-main">Glutamate receptor</span> Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells

Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

<span class="mw-page-title-main">Causes of autism</span> Proposed causes of autism

The causes of autism are environmental or genetic factors that predispose an individual to develop autism, also known as autism spectrum disorder (ASD). Many causes of autism have been proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction and restricted/repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals.

Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances from leaving the intestine and migrating to the body more widely. In a healthy human intestine, small particles can migrate through tight junction claudin pore pathways, and particles up to 10–15 Å can transit through the paracellular space uptake route. There is some evidence abnormally increased intestinal permeability may play a role in some chronic diseases and inflammatory conditions. The most well understood condition with observed increased intestinal permeability is celiac disease.

<span class="mw-page-title-main">Wheat allergy</span> Medical condition

Wheat allergy is an allergy to wheat which typically presents itself as a food allergy, but can also be a contact allergy resulting from occupational exposure. Like all allergies, wheat allergy involves immunoglobulin E and mast cell response. Typically the allergy is limited to the seed storage proteins of wheat. Some reactions are restricted to wheat proteins, while others can react across many varieties of seeds and other plant tissues. Wheat allergy is rare. Prevalence in adults was found to be 0.21% in a 2012 study in Japan.

<span class="mw-page-title-main">Triticeae glutens</span> Seed storage protein in mature wheat seeds

Gluten is the seed storage protein in mature wheat seeds. It is the sticky substance in bread wheat which allows dough to rise and retain its shape during baking. The same, or very similar, proteins are also found in related grasses within the tribe Triticeae. Seed glutens of some non-Triticeae plants have similar properties, but none can perform on a par with those of the Triticeae taxa, particularly the Triticum species. What distinguishes bread wheat from these other grass seeds is the quantity of these proteins and the level of subcomponents, with bread wheat having the highest protein content and a complex mixture of proteins derived from three grass species.

<i>N</i>-Acetylaspartylglutamic acid Peptide neurotransmitter

N-Acetylaspartylglutamic acid is a peptide neurotransmitter and the third-most-prevalent neurotransmitter in the mammalian nervous system. NAAG consists of N-acetylaspartic acid (NAA) and glutamic acid coupled via a peptide bond.

<span class="mw-page-title-main">Gluten-related disorders</span> Set of diseases caused by gluten exposure

Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.

The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are four types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.

<span class="mw-page-title-main">Clinical neurochemistry</span>

Clinical neurochemistry is the field of neurological biochemistry which relates biochemical phenomena to clinical symptomatic manifestations in humans. While neurochemistry is mostly associated with the effects of neurotransmitters and similarly functioning chemicals on neurons themselves, clinical neurochemistry relates these phenomena to system-wide symptoms. Clinical neurochemistry is related to neurogenesis, neuromodulation, neuroplasticity, neuroendocrinology, and neuroimmunology in the context of associating neurological findings at both lower and higher level organismal functions.

The causes of schizophrenia that underlie the development of schizophrenia, a psychiatric disorder, are complex and not clearly understood. A number of hypotheses including the dopamine hypothesis, and the glutamate hypothesis have been put forward in an attempt to explain the link between altered brain function and the symptoms and development of schizophrenia.

The opioid excess theory is a theory which postulates that autism is the result of a metabolic disorder in which opioid peptides produced through metabolism of gluten and casein pass through an abnormally permeable intestinal membrane and then proceed to exert an effect on neurotransmission through binding with opioid receptors. It is believed by advocates of this hypothesis that autistic children are unusually sensitive to gluten, which results in small bowel inflammation in these children, which in turn allows these opioid peptides to enter the brain.

References

  1. Pruimboom L, de Punder K (November 2015). "The opioid effects of gluten exorphins: asymptomatic celiac disease". Journal of Health, Population, and Nutrition. 33 (1): 24. doi: 10.1186/s41043-015-0032-y . PMC   5025969 . PMID   26825414.
  2. Teschemacher H (2003-06-01). "Opioid receptor ligands derived from food proteins". Current Pharmaceutical Design. 9 (16): 1331–44. doi:10.2174/1381612033454856. PMID   12769741.
  3. Yoshikawa M (2013). "Chapter 214: Exorphins". In Kastin AJ (ed.). Handbook of Biologically Active Peptides (2nd ed.). Academic Press. pp. 1570–1576. ISBN   978-0-12-385096-6.
  4. Brudnak MA, Rimland B, Kerry RE, Dailey M, Taylor R, Stayton B, et al. (May 2002). "Enzyme-based therapy for autism spectrum disorders -- is it worth another look?". Medical Hypotheses. 58 (5): 422–8. doi:10.1054/mehy.2001.1513. PMID   12056881.
  5. Dohan FC (1988-01-01). "Genetic hypothesis of idiopathic schizophrenia: its exorphin connection". Schizophrenia Bulletin. 14 (4): 489–94. doi: 10.1093/schbul/14.4.489 . PMID   2851166.