Cholecystokinin

Cholecystokinin, often abbreviated as CCK, is a peptide hormone secreted from mucosal epithelial cells in the duodenum, the first portion of the small intestine. CCK is an important facilitator of digestion in the small intestine. CCK helps deliver digestive enzymes from the pancreas and bile from the gallbladder into the small intestine. The hormone is secreted by neurons in the enteric nervous system, the localized nervous system of the digestive system. CCK is also found throughout the brain, and it is one of the most essential human brain peptides.

Brief History

Andrew Conway Ivy, Eric Goldberg, Harold C. Lueth, and Grant Kloster discovered CCK in 1928 during their studies in gallbladder contraction and evacuation. The team realized a substance was being released by the small intestine after the ingestion of fat, causing the gallbladder to contract. More than a decade later, another research group discovered a substance causing pancreatic enzyme secretion similar to that found in the gallbladder. CCK was simply identified as a hormone mechanism up until the 1960s, and it was later referred to as pancreozymin due to its activity within the pancreas. In the 1970s, a group of scientists proved that a single peptide hormone containing thirty-three amino acids was stimulating both the pancreatic and gallbladder functions. Originally misidentified as another similarly structured gastrointestinal hormone—gastrin—the hormone was eventually identified as CCK. Studies showed CCK was abundant in the brain and gastrointestinal system and could contain varying numbers of amino acids, a component of protein in blood cells.

Cholecystokinin, like gastrin, is a linear peptide, meaning its amino acids form a single extending chain along the peptide. It is synthesized by preprohormone, the precursor of the protein prohormone, which is the precursor to a peptide hormone. The preprohormone protein reacts with water and is chemically broken down into peptides and amino acids, resulting in a family of peptides with amino acid chains, each ending in the same carboxyl acid group. The biological activity of CCK lies within this carboxyl group, also referred to as the C-terminus group. Each CCK hormone contains a different number of amino acids, and this number identifies the form of CCK being observed—for example, CCK8 and CCK33. The number of amino acids attached to CCK depends on how its proteins are modified during protein synthesis. In all CCK peptides, the amino acid tyrosine, located seven spaces from the end of the amino acid chain, is combined with sulfuric acid, a necessary component of CCK's biological activity.

CCK receptors are located in the pancreas, stomach, and brain. Two types of CCK receptors exist: CCKA and CCKB. CCKA is most commonly found on pancreatic acinar cells. CCKB, also a gastrin receptor, is primarily found in the brain and stomach. The specific structure of a CCK amino acid chain dictates how the hormone fits into these receptors. CCKA and CCKB receptors are G-protein-coupled receptors, the largest group of membrane receptors in eukaryotic, or multi-celled, organisms. Like most G-protein-coupled receptors, they have seven transmembrane domains, which means their amino acid chains can wind through a cell membrane seven times.

Overview

CCK plays an important role in the digestion of food. Food macromolecules—such as proteins, polysaccharides, and triglycerides—flow into the small intestine, where they are digested and synthesized into absorbable nutrients, such as amino acids, monosaccharides, and fatty acids. Successful digestion of these nutrients relies on the transport of digestive enzymes and liver bile salts delivered from the pancreas and gallbladder into the small intestine. CCK is crucial to the transport of these substances from the pancreas and gallbladder. CCK secretion is incited by the presence of partially digested fats and proteins in these areas. Once there is enough CCK in the blood, pancreatic enzymes are released, and the gallbladder contracts to deliver bile into the duodenum.

Once the pancreatic digestive enzymes and bile are released, they pass through the small intestine and begin to break down the fat and protein molecules that stimulated CCK secretion to begin with. This leads to digestion and absorption of the remaining nutrients. Once this process is complete, secretion of CCK stops. Some studies have suggested CCK can help regulate appetite. Injection of CCK into the brains of laboratory animals has been shown to reduce hunger. Further experimentation showed that though CCK may play a role in appetite control, it is likely only a minor one.

CCK is also found in the neurons of the small intestinal wall and in many parts of the brain, acting as neuropeptides, or neurotransmitters, a chemical that carries communications between nerve cells and muscles. Despite knowing that CCK is one of the most abundant neuropeptides in the central nervous system, scientists understand little about the role CCK plays in brain function.

Although it is rare, improper secretion of CCK can lead to health issues. CCK deficiency can contribute to autoimmune polyendocrine syndrome (ASP), a rare disease that primarily affects the function of the endocrine system, which deals with the secretion of hormones into the blood. CCK deficiency has also been linked to exocrine pancreatic insufficiency (EPI), a condition that prevents a person from digesting food properly. In relation to CCK's function in the brain, evidence suggests abnormal expression of CCK or its brain receptors can lead to the development of mental health disorders, such as anxiety and schizophrenia. A great deal of evidence exists linking CCK to panic disorder, a condition characterized by panic attacks, anxiety, and avoidance behavior. Some research has indicated that CCK is linked to the neuronal network that facilitates feelings of fear in the brain. Studies have also suggested mutations in CCK could be responsible for hallucinations among individuals with Parkinson's disease.

Bibliography

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"Cholecystokinin." U.S. National Library of Medicine, meshb.nlm.nih.gov/record/ui?name=Cholecystokinin. Accessed 26 June 2017.

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