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Pathway Description
Gastric Acid Production
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2018-09-10
Last Updated: 2019-08-16
Gastric acid plays a key role in the digestion of proteins by activating digestive enzymes to break down long chains of amino acids. In addition, it aids in the absorption of certain vitamins and minerals and also acts as one of the body's first line of defence by killing ingested micro-organisms. This digestive fluid is formed in the stomach (specifically by the parietal cells) and is mainly composed of hydrochloric acid (HCl). However, it is also constituted of potassium chloride (KCl) and sodium chloride (NaCl). The main stimulants of acid secretion are histamine, gastrin, and acetylcholine which all, after binding to their respective receptors on the parietal cell membrane, trigger a G-protein signalling cascade that causes the activation of the H+/K+ ATPase proton pump. As a result, hydrogen ions are able to be pumped out of the parietal cell and into the lumen of the stomach. The hydrogen ions are available inside the parietal cell after water and carbon dioxide combine to form carbonic acid(the reaction is catalyzed by the carbonic anhydrase enzyme) which dissociates into a bicarbonate ion and a hydrogen ion. Moreover, the chloride and potassium ions are transported into the stomach lumen through their own channels so that hydrogen ions and/or potassium ions can form an ionic bond with chloride ions to form HCl and/or KCl, which are both constituents of stomach acid. In addition, the peptide hormone somatostatin is the main inhibitor to gastric acid secretion. Not only does it inhibit the G-protein signalling cascade that leads to proton pump activation, but it also directly acts on the enterochromaffin-like cells and G cells to inhibit histamine and gastrin release, respectively.
References
Gastric Acid Production References
Fraser PJ, Curtis PJ: Molecular evolution of the carbonic anhydrase genes: calculation of divergence time for mouse carbonic anhydrase I and II. J Mol Evol. 1986;23(4):294-9.
Pubmed: 3104601
Fraser P, Cummings P, Curtis P: The mouse carbonic anhydrase I gene contains two tissue-specific promoters. Mol Cell Biol. 1989 Aug;9(8):3308-13. doi: 10.1128/mcb.9.8.3308.
Pubmed: 2571923
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014.
Pubmed: 16141072
Morley GP, Callaghan JM, Rose JB, Toh BH, Gleeson PA, van Driel IR: The mouse gastric H,K-ATPase beta subunit. Gene structure and co-ordinate expression with the alpha subunit during ontogeny. J Biol Chem. 1992 Jan 15;267(2):1165-74.
Pubmed: 1370459
Canfield VA, Levenson R: Structural organization and transcription of the mouse gastric H+, K(+)-ATPase beta subunit gene. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8247-51. doi: 10.1073/pnas.88.18.8247.
Pubmed: 1654563
Mathews PM, Claeys D, Jaisser F, Geering K, Horisberger JD, Kraehenbuhl JP, Rossier BC: Primary structure and functional expression of the mouse and frog alpha-subunit of the gastric H(+)-K(+)-ATPase. Am J Physiol. 1995 May;268(5 Pt 1):C1207-14. doi: 10.1152/ajpcell.1995.268.5.C1207.
Pubmed: 7762614
Friedli M, Guipponi M, Bertrand S, Bertrand D, Neerman-Arbez M, Scott HS, Antonarakis SE, Reymond A: Identification of a novel member of the CLIC family, CLIC6, mapping to 21q22.12. Gene. 2003 Nov 27;320:31-40. doi: 10.1016/s0378-1119(03)00830-8.
Pubmed: 14597386
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Melvin JE, Park K, Richardson L, Schultheis PJ, Shull GE: Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)/H(+) exchanger. J Biol Chem. 1999 Aug 6;274(32):22855-61. doi: 10.1074/jbc.274.32.22855.
Pubmed: 10428871
Chavez JC, Hernandez-Gonzalez EO, Wertheimer E, Visconti PE, Darszon A, Trevino CL: Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation. Biol Reprod. 2012 Jan 19;86(1):1-14. doi: 10.1095/biolreprod.111.094037. Print 2012 Jan.
Pubmed: 21976599
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26.
Pubmed: 19468303
Kobayashi T, Inoue I, Jenkins NA, Gilbert DJ, Copeland NG, Watanabe T: Cloning, RNA expression, and chromosomal location of a mouse histamine H2 receptor gene. Genomics. 1996 Nov 1;37(3):390-4. doi: 10.1006/geno.1996.0575.
Pubmed: 8938453
Koh TJ, Wang TC: Molecular cloning and sequencing of the murine gastrin gene. Biochem Biophys Res Commun. 1995 Nov 2;216(1):34-41. doi: 10.1006/bbrc.1995.2588.
Pubmed: 7488110
Noh MJ, Kim SJ, Kang YK, Yoo OJ: Sequences responsible for transcription termination of the mouse gastrin gene. Biochem Mol Biol Int. 1995 May;35(6):1205-13.
Pubmed: 7492958
Friis-Hansen L, Rourke IJ, Bundgaard JR, Rehfeld JF, Samuelson LC: Molecular structure and genetic mapping of the mouse gastrin gene. FEBS Lett. 1996 May 20;386(2-3):128-32. doi: 10.1016/0014-5793(96)00430-9.
Pubmed: 8647266
Lay JM, Jenkins C, Friis-Hansen L, Samuelson LC: Structure and developmental expression of the mouse CCK-B receptor gene. Biochem Biophys Res Commun. 2000 Jun 16;272(3):837-42. doi: 10.1006/bbrc.2000.2875.
Pubmed: 10860839
Fuhrmann G, Heilig R, Kempf J, Ebel A: Nucleotide sequence of the mouse preprosomatostatin gene. Nucleic Acids Res. 1990 Mar 11;18(5):1287. doi: 10.1093/nar/18.5.1287.
Pubmed: 1969620
Samson WK, Zhang JV, Avsian-Kretchmer O, Cui K, Yosten GL, Klein C, Lyu RM, Wang YX, Chen XQ, Yang J, Price CJ, Hoyda TD, Ferguson AV, Yuan XB, Chang JK, Hsueh AJ: Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions. J Biol Chem. 2008 Nov 14;283(46):31949-59. doi: 10.1074/jbc.M804784200. Epub 2008 Aug 26.
Pubmed: 18753129
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000589
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