Big gastrin

Last updated
Big Gastrin
Big gastrin.png
Names
IUPAC name
H-Pyr-Leu-Gly-Gly-Gln-Gly-Pro-Gly-Gly-Gly-Gly-Ala-Asp-Gly-Gly-Lys-Lys-Gln-Gly-Pro-Gly-Gly-Glu-Glu-Glu-Glu-Gly-Ala-Gly-Gly-Trp-Met-Asp-Phe-NH2
Systematic IUPAC name
L-pyroglutamyl-L-leucyl-glycyl-glycyl-L-glutaminyl-glycyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-alanyl-L-alpha-aspartyl-glycyl-glycyl-L-lysyl-L-lysyl-L-glutaminyl-glycyl-L-prolyl-glycyl-glycyl-L-alpha-glutamyl-L-alpha-glutamyl-L-alpha-glutamyl-L-alpha-glutamyl-glycyl-L-alanyl-glycyl-glycyl-L-tryptophyl-L-methionyl-L-alpha-aspartyl-L-phenylalaninamide
Other names
Pro-gastrin, Big-Gastrin, G-34, Gastrin-34
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
UNII
  • InChI=1S/C132H194N40O49S/c1-66(2)45-84(169-125(214)78-27-34-92(175)156-78)120(209)147-54-96(179)143-60-103(186)158-75(25-32-90(135)173)117(206)152-64-106(189)171-42-15-23-88(171)131(220)150-56-98(181)140-51-93(176)139-52-94(177)141-58-100(183)155-68(4)116(205)168-86(48-112(199)200)121(210)148-55-97(180)142-59-102(185)157-73(21-11-13-40-133)122(211)161-74(22-12-14-41-134)123(212)162-76(26-33-91(136)174)119(208)153-65-107(190)172-43-16-24-89(172)132(221)151-57-99(182)144-61-104(187)159-79(29-36-109(193)194)124(213)164-81(31-38-111(197)198)127(216)165-80(30-37-110(195)196)126(215)163-77(28-35-108(191)192)118(207)149-63-101(184)154-67(3)115(204)146-53-95(178)145-62-105(188)160-85(47-70-50-138-72-20-10-9-19-71(70)72)129(218)166-82(39-44-222-5)128(217)170-87(49-113(201)202)130(219)167-83(114(137)203)46-69-17-7-6-8-18-69/h6-10,17-20,50,66-68,73-89,138H,11-16,21-49,51-65,133-134H2,1-5H3,(H2,135,173)(H2,136,174)(H2,137,203)(H,139,176)(H,140,181)(H,141,177)(H,142,180)(H,143,179)(H,144,182)(H,145,178)(H,146,204)(H,147,209)(H,148,210)(H,149,207)(H,150,220)(H,151,221)(H,152,206)(H,153,208)(H,154,184)(H,155,183)(H,156,175)(H,157,185)(H,158,186)(H,159,187)(H,160,188)(H,161,211)(H,162,212)(H,163,215)(H,164,213)(H,165,216)(H,166,218)(H,167,219)(H,168,205)(H,169,214)(H,170,217)(H,191,192)(H,193,194)(H,195,196)(H,197,198)(H,199,200)(H,201,202)/t67-,68-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-/m0/s1 Yes check.svgY
    Key: RZIMNEGTIDYAGZ-HNSJZBNRSA-N Yes check.svgY
  • InChI=1/C132H194N40O49S/c1-66(2)45-84(169-125(214)78-27-34-92(175)156-78)120(209)147-54-96(179)143-60-103(186)158-75(25-32-90(135)173)117(206)152-64-106(189)171-42-15-23-88(171)131(220)150-56-98(181)140-51-93(176)139-52-94(177)141-58-100(183)155-68(4)116(205)168-86(48-112(199)200)121(210)148-55-97(180)142-59-102(185)157-73(21-11-13-40-133)122(211)161-74(22-12-14-41-134)123(212)162-76(26-33-91(136)174)119(208)153-65-107(190)172-43-16-24-89(172)132(221)151-57-99(182)144-61-104(187)159-79(29-36-109(193)194)124(213)164-81(31-38-111(197)198)127(216)165-80(30-37-110(195)196)126(215)163-77(28-35-108(191)192)118(207)149-63-101(184)154-67(3)115(204)146-53-95(178)145-62-105(188)160-85(47-70-50-138-72-20-10-9-19-71(70)72)129(218)166-82(39-44-222-5)128(217)170-87(49-113(201)202)130(219)167-83(114(137)203)46-69-17-7-6-8-18-69/h6-10,17-20,50,66-68,73-89,138H,11-16,21-49,51-65,133-134H2,1-5H3,(H2,135,173)(H2,136,174)(H2,137,203)(H,139,176)(H,140,181)(H,141,177)(H,142,180)(H,143,179)(H,144,182)(H,145,178)(H,146,204)(H,147,209)(H,148,210)(H,149,207)(H,150,220)(H,151,221)(H,152,206)(H,153,208)(H,154,184)(H,155,183)(H,156,175)(H,157,185)(H,158,186)(H,159,187)(H,160,188)(H,161,211)(H,162,212)(H,163,215)(H,164,213)(H,165,216)(H,166,218)(H,167,219)(H,168,205)(H,169,214)(H,170,217)(H,191,192)(H,193,194)(H,195,196)(H,197,198)(H,199,200)(H,201,202)/t67-,68-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-/m0/s1
    Key: RZIMNEGTIDYAGZ-HNSJZBNRBP
  • CC(C)CC(C(=O)NCC(=O)NCC(=O)NC(CCC(=O)N)C(=O)NCC(=O)N1CCCC1C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)NC(C)C(=O)NC(CC(=O)O)C(=O)NCC(=O)NCC(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCC(=O)N)C(=O)NCC(=O)N2CCCC2C(=O)NCC(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NCC(=O)NC(C)C(=O)NCC(=O)NCC(=O)NC(Cc3c[nH]c4c3cccc4)C(=O)NC(CCSC)C(=O)NC(CC(=O)O)C(=O)NC(Cc5ccccc5)C(=O)N)NC(=O)C6CCC(=O)N6
Properties
C132H194N40O49S
Molar mass 3157.26 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Big gastrin (G-34) is a form of gastrin with 34 amino acids in its sequence. Big gastrin is a hormone produced by G cells and can be found inside of the stomach. [1] G-34 promotes the secretion of gastric acid in dogs. [2] In dogs, the half life of this peptide is between 14.7 and 16.8 minutes. [3] In humans, an over production of this hormone by gastrinomas leads to Zollinger-Ellison Syndrome. [4]

Big Gastrin Responses to Foods:

Big gastrin (G34) is one form of gastrin predominate in circulation after a meal, another major form is called little gastrin (G17). Both forms of gastrin have been isolated from human gastrinoma and hog antral mucosa. [5] G34 is carboxy-amidated and can be sulphated or unsulphated at the tyrosine residues. [6] Binding of gastrin to the receptors in stomach can cause the secretion of hydrochloric acids (HCl), the gastric acid. [7] Duodenal ulcer patients tend to have higher than normal basal and maximal rate of gastric acid secretion, while gastric ulcer patients have lower than normal basal and maximal of gastric acid output. [8] Comparing G34 in normal and peptic ulcer subjects by using radioimmunoassay in fasting serum and after feeding, basal G34 was found similar in normal and duodenal ulcer but raised in gastric ulcer before meal. After a meal, the concentration of G34 was increased in both duodenal ulcer patients and gastric ulcer patients, which significantly higher than normal people. [6]

Related Research Articles

<span class="mw-page-title-main">Stomach</span> Digestive organ

The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach is involved in the gastric phase of digestion, following chewing. It performs a chemical breakdown by means of enzymes and hydrochloric acid.

Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating. With a gastric ulcer, the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of cases.

<span class="mw-page-title-main">Zollinger–Ellison syndrome</span> Condition in which tumours stimulate excessive gastric acid production

Zollinger–Ellison syndrome is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea.

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

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

<span class="mw-page-title-main">Gastric acid</span> Digestive fluid formed in the stomach

Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the long chains of amino acids of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce mucus – a viscous barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to neutralize gastric acid passing into the digestive tract.

<span class="mw-page-title-main">Parietal cell</span> Epithelial cell in the stomach

Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the stomach. They contain an extensive secretory network of canaliculi from which the HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a concentration gradient of about 3 million to 1, which is the steepest ion gradient formed in the human body. Parietal cells are primarily regulated via histamine, acetylcholine and gastrin signalling from both central and local modulators.

<span class="mw-page-title-main">Esophagogastroduodenoscopy</span> Diagnostic endoscopic procedure

Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered a minimally invasive procedure since it does not require an incision into one of the major body cavities and does not require any significant recovery after the procedure. However, a sore throat is common.

<span class="mw-page-title-main">Atrophic gastritis</span> Medical condition

Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency possibly leading to pernicious anemia; and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with autoimmune atrophic gastritis (Type A gastritis) are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.

<span class="mw-page-title-main">Multiple endocrine neoplasia type 1</span> Medical condition

Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. Individuals suffering from this disorder are prone to developing multiple endocrine and nonendocrine tumors. It was first described by Paul Wermer in 1954.

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

Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.

<span class="mw-page-title-main">Gastric glands</span> Glands in lining of the human stomach

The gastric glands are glands in the lining of the stomach that play an essential role in the process of digestion. All of the glands have mucus-secreting foveolar cells. Mucus lines the entire stomach, and protects the stomach lining from the effects of hydrochloric acid released from other cells in the glands.

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

Enprostil is a synthetic prostaglandin designed to resemble dinoprostone. Enprostil was found to be a highly potent inhibitor of gastric HCl secretion. It is an analog of prostaglandin E2 but unlike this prostaglandin, which binds to and activates all four cellular receptors viz., EP1, EP2, EP3, and EP4 receptors, enprostil is a more selective receptor agonist in that it binds to and activates primarily the EP3 receptor. Consequently, enprostil is expected to have a narrower range of actions that may avoid some of the unwanted side-effects and toxicities of prostaglandin E2. A prospective multicenter randomized controlled trial conducted in Japan found combining enprostil with cimetidine was more effective than cimetidine alone in treating gastric ulcer.

Timeline of peptic ulcer disease and <i>Helicobacter pylori</i>

This is a timeline of the events relating to the discovery that peptic ulcer disease and some cancers are caused by H. pylori. In 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery that peptic ulcer disease (PUD) was primarily caused by Helicobacter pylori, a bacterium with affinity for acidic environments, such as the stomach. As a result, PUD that is associated with H. pylori is currently treated with antibiotics used to eradicate the infection. For decades prior to their discovery, it was widely believed that PUD was caused by excess acid in the stomach. During this time, acid control was the primary method of treatment for PUD, to only partial success. Among other effects, it is now known that acid suppression alters the stomach milieu to make it less amenable to H. pylori infection.

<span class="mw-page-title-main">Enteroendocrine cell</span>

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

A bland diet is a diet consisting of foods that are generally soft, low in dietary fiber, cooked rather than raw, and not spicy. It is an eating plan that emphasizes foods that are easy to digest. It is commonly recommended for people recovering from surgery or conditions affecting the gastrointestinal tract.

The nervous system, and endocrine system collaborate in the digestive system to control gastric secretions, and motility associated with the movement of food throughout the gastrointestinal tract, including peristalsis, and segmentation contractions.

Hilda Tracy worked at University of Liverpool, UK, with Rod Gregory FRS to isolate and characterise the gastrointestinal hormone gastrin. She led the structure-function studies and had the first insight into gastrin's role in the clinical pathology of pancreatic Zollinger-Ellison tumours.

<span class="mw-page-title-main">Acid peptic diseases</span> Overview of the acid peptic diseases of the stomach and gastrointestinal tract

Acid peptic diseases, such as peptic ulcers, Zollinger-Ellison syndrome, and gastroesophageal reflux disease, are caused by distinct but overlapping pathogenic mechanisms involving acid effects on mucosal defense. Acid reflux damages the esophageal mucosa and may also cause laryngeal tissue injury, leading to the development of pulmonary symptoms.

Sir Andrew Watt Kay FRSE, FRCPSG, FRCSEd was a Scottish academic surgeon who was Regius Professor of Surgery at the University of Glasgow from 1964 to 1981. He developed the augmented histamine test, which bore his name, and was widely used in the investigation and treatment of peptic ulcer disease. He was knighted for services to surgery. From 1972 to 1974 he served as president of the Royal College of Physicians and Surgeons of Glasgow.

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

Antrectomy, also called distal gastrectomy, is a type of gastric resection surgery that involves the removal of the stomach antrum to treat gastric diseases causing the damage, bleeding, or blockage of the stomach. This is performed using either the Billroth I (BI) or Billroth II (BII) reconstruction method. Quite often, antrectomy is used alongside vagotomy to maximise its safety and effectiveness. Modern antrectomies typically have a high success rate and low mortality rate, but the exact numbers depend on the specific conditions being treated.

References

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  2. Walsh, J. H; Debas, H. T; Grossman, M. I (1974). "Pure human big gastrin. Immunochemical properties, disappearance half time, and acid-stimulating action in dogs". The Journal of Clinical Investigation. 54 (2): 477–85. doi:10.1172/JCI107783. PMC   301575 . PMID   4847254.
  3. Walsh, John H.; Debas, Haile T.; Grossman, Morton I. (1974-08-01). "Pure Human Big Gastrin IMMUNOCHEMICAL PROPERTIES, DISAPPEARANCE HALF TIME, AND ACID-STIMULATING ACTION IN DOGS". Journal of Clinical Investigation. 54 (2): 480. doi:10.1172/jci107783. ISSN   0021-9738. PMC   301575 . PMID   4847254.
  4. National Digestive Diseases Information Clearinghouse (U.S.) (2009). Digestive diseases dictionary. U.S. Dept. of Health and Human Services, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse. OCLC   44203071.
  5. Gregory, R.A.; Tracy, H.J. (1964). "The constitution and properties of two gastrins extracted from hog antral mucosa. Part 1". The Isolation of Two Gastrins from Hog Antral Mucosa: Gut 5, 103–115.
  6. 1 2 I.L., Taylor; G.J., Dockary; J., Calam; R.J., Walker (1979). "Big and little gastrin responses to food in normal and ulcer subjects" (PDF). Department of Physiology. Gut. University of Liverpool, and The Gastrointestinal Unit, Walton Hospital, Liverpool. 20 (11): Gut, 957–962. doi:10.1136/gut.20.11.957. PMC   1412672 . PMID   527872.
  7. Abdul M., CHOUDHURY; George W., KENNER †; Stanley, MOORE; Kuzhalmannan L., RAMACHANDRAN; Warwick D., THORPE; Robert, RAMAGE; Graham J., DOCKRAY (1980). "N-Terminal Sequence of Human Big Gastrin: Sequence, Synthetic and Immunochemical Studies". 361: Issue 2.{{cite journal}}: Cite journal requires |journal= (help)
  8. Wormsley, K. G.; Grossman, M.I. (1965). "Maximal histolog test in control subjects and patients with peptic ulcer": Gut, 6, 427–435.{{cite journal}}: Cite journal requires |journal= (help)