Little gastrin I

Little gastrin I
Names
Other names
Gastrin I; Human gastrin I; pGlu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 233-157-0
UNII
  • InChI=1S/C97H124N20O31S/c1-49(2)39-68(114-95(146)71(43-54-46-100-59-18-11-9-16-57(54)59)116-97(148)73-19-12-37-117(73)76(121)48-102-85(136)60-24-30-74(119)104-60)93(144)110-65(29-35-81(130)131)91(142)109-64(28-34-80(128)129)90(141)108-63(27-33-79(126)127)89(140)107-62(26-32-78(124)125)88(139)106-61(25-31-77(122)123)87(138)103-50(3)84(135)113-69(41-52-20-22-55(118)23-21-52)86(137)101-47-75(120)105-70(42-53-45-99-58-17-10-8-15-56(53)58)94(145)111-66(36-38-149-4)92(143)115-72(44-82(132)133)96(147)112-67(83(98)134)40-51-13-6-5-7-14-51/h5-11,13-18,20-23,45-46,49-50,60-73,99-100,118H,12,19,24-44,47-48H2,1-4H3,(H2,98,134)(H,101,137)(H,102,136)(H,103,138)(H,104,119)(H,105,120)(H,106,139)(H,107,140)(H,108,141)(H,109,142)(H,110,144)(H,111,145)(H,112,147)(H,113,135)(H,114,146)(H,115,143)(H,116,148)(H,122,123)(H,124,125)(H,126,127)(H,128,129)(H,130,131)(H,132,133)/t50-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-/m0/s1
    Key: GKDWRERMBNGKCZ-RNXBIMIWSA-N
  • C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)NCC(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC4=CC=CC=C4)C(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@@H]7CCCN7C(=O)CNC(=O)[C@@H]8CCC(=O)N8
Properties
C97H124N20O31S
Molar mass 2098.20 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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Infobox references

Little gastrin I also known as '''gastrin-17''' or ''G-17''', is a 17-amino acid Peptide hormone and the most abundant form of gastrin found in healthy individuals.[1][2]It is produced primarily by G-cells in the Gastric antrum and plays a key role in regulating gastric acid secretion and digestion[3].

The existence of gastrin was first proposed by British physiologist John Sydney Edkins in 1905, though its structure was not fully worked out until the 1960s[4]. Little gastrin I is synthesized from a larger precursor protein called preprogastrin, which undergoes several processing steps before producing the mature hormone[5]. It stimulates parietal cells in the stomach to secrete hydrochloric acid and is involved in gastric motility and the release of pepsin and intrinsic factor[3]. Its release is triggered by food intake and inhibited by low stomach pH, forming a negative feedback loop[6]. Abnormally high levels of gastrin, known as hypergastrinemia, are associated with conditions such as atrophic gastritis, pernicious anemia, and gastric cancer[7].

History

The idea that the stomach produces a hormone to trigger acid secretion was first put forward by British physiologist John Sydney Edkins in 1905. Working with cats, he found that injecting extracts from the stomach lining causes an increase in acid production, and he called the substance responsible "gastrin"[4]. His theory was met with skepticism after histamine was discovered in 1910, as it had a similar effect on the stomach, leading many scientists to doubt whether gastrin was a separate hormone at all[4].

The debate was largely settled in 1942, when Simon Komarov published research showing that a gastrin extract could stimulate acid secretion on its own, separate from histamine[8]. Building on this work, Roderic Gregory and Hilda Tracy isolated the hormone in purified form in the early 1960s and identified two closely related versions, which they named gastrin I and gastrin II[8]. Chemist George Kenner then determined the full amino acid sequence of both peptides, making gastrin the first gut hormone to have its complete structure worked out[8].

Biosynthesis

Little gastrin I is synthesized from a 101-amino acid precursor protein called preprogastrin[5]. A signal peptide of 21 amino acids is removed in the Endoplasmic reticulum, producing the 80-amino acid intermediate progastrin[5]. Progastrin is then cleaved at specific site by Proprotein convertase as it moves through the Golgi apparatus toward secretory vesicles, producing gastrin-34 and gastrin-17 as the two major biologically active end products[9]. In the normal human stomach, around 85% of amidated gastrin in the antral mucosa is in the G-17 form[9].

Structure

Little gastrin I consists of 17 amino acids with an amidated C-terminus. It is derived from a larger precursor molecule, preprogastrin, which undergoes several processing steps before producing the mature hormone[5]. Gastrin II has identical amino acid composition to Gastrin I, the only difference is that the single tyrosine residue is sulfated in Gastrin II.[10]

Function

Little gastrin I stimulates Parietal cell in the stomach to secrete Hydrochloric acid.[3] It does this partly by binding directly to Cholecystokinin B receptor on parietal cells, and partly by triggering Enterochromaffin-like cell to release Histamine, which then acts on parietal cells.[3] Beyond acid secretion, it also plays a role in gastric motility and then release of Pepsin and Intrinsic factor[5].

Secretion and Regulation

Release of little gastrin I is triggered by the presence of proteins and amino acids in the stomach, gastric distension as well as elevated stomach pH[3]. The release is also promoted by vagal nerve stimulation[3]. Secretion is inhibited by Somatostatin and by acidic gastric pH. This forms a negative feedback loop[6]. Its half-life in circulation is short, around 3-7 minutes, after which it is mainly broken down by the kidneys [2].

Clinical Significance

Abnormally high levels of gastrin, known as Hypergastrinemia, can result from conditions such as Atrophic gastritis and Pernicious anemia[7]. Gastrin-17 has also been studied in relation to gastric cancer, as elevated levels may contribute to tumor growth in the stomach lining[7].

References

  1. ^ Mutt, Viktor (2013-10-22). Gastrointestinal Hormones: Advances in Metabolic Disorders. Academic Press. ISBN 978-1-4832-1553-2.
  2. ^ a b Varro, Andrea; Ardill, Joy ES (2003-09-01). "Gastrin: an analytical review". Annals of Clinical Biochemistry: International Journal of Laboratory Medicine. 40 (5): 472–480. doi:10.1258/000456303322326380. ISSN 0004-5632. PMID 14503984.
  3. ^ a b c d e f Prosapio, Jordon G.; Sankar, Parvathy; Jialal, Ishwarlal (2026), "Physiology, Gastrin", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30521243, retrieved 2026-05-03
  4. ^ a b c Modlin, Irvin M.; Kidd, Mark; Marks, I. N.; Tang, Laura H. (February 1997). "The pivotal role of John S. Edkins in the discovery of gastrin". World Journal of Surgery. 21 (2): 226–234. doi:10.1007/s002689900221. ISSN 0364-2313. PMID 8995084.
  5. ^ a b c d e Dockray, G J; Varro, A; Dimaline, R; Wang, T (March 2001). "The Gastrins: Their Production and Biological Activities". Annual Review of Physiology. 63 (1): 119–139. doi:10.1146/annurev.physiol.63.1.119. ISSN 0066-4278. PMID 11181951.
  6. ^ a b Schubert, Mitchell L. (November 2016). "Gastric acid secretion". Current Opinion in Gastroenterology. 32 (6): 452–460. doi:10.1097/MOG.0000000000000308. ISSN 0267-1379. PMID 27607343.
  7. ^ a b c Copps, Jeffrey; Murphy, Richard; Lovas, Sandor (2009-12-01). "The Production and Role of Gastrin-17 and Gastrin-17-Gly in Gastrointestinal Cancers". Protein & Peptide Letters. 16 (12): 1504–1518. doi:10.2174/092986609789839269. PMC 2872940. PMID 20001914.
  8. ^ a b c Duan, Suzann; Rico, Karen; Merchant, Juanita L (January 2022). "Gastrin: From Physiology to Gastrointestinal Malignancies". Function. 3 (1) zqab062. doi:10.1093/function/zqab062. PMC 8788842. PMID 35330921.
  9. ^ a b Rehfeld, Jens F. (2021-06-29). "Gastrin and the Moderate Hypergastrinemias". International Journal of Molecular Sciences. 22 (13): 6977. doi:10.3390/ijms22136977. ISSN 1422-0067. PMC 8269006. PMID 34209478.
  10. ^ Gastrin. University of California Press. 1966-01-01.


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