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Pathway Description
Lactose Intolerance
Homo sapiens
Disease Pathway
Created: 2013-08-19
Last Updated: 2022-10-18
Lactose intolerance is a condition in which the body does not support the ingestion of lactose through the consumption of milk, cheese, and other dairy products. This intolerance occurs due to the lack of the enzyme intestinal lactase, which is an enzyme found in newborns. The frequency of this enzyme declines rapidly after the child stops breastfeeding. Lactase deficiency is most prevalent in Asia, Africa and Indigenous populations in North and South America. The symptoms of lactose intolerance include diarrhea, bloating, abdominal pain and excessive flatus. The cause of these symptoms is the processing of the ingested lactose being fermented by intestinal bacteria instead of in the small intestine, where lactose is meant to be processed.
References
Lactose Intolerance References
Vandenplas Y: Lactose intolerance. Asia Pac J Clin Nutr. 2015;24 Suppl 1:S9-13.
Pubmed: 26715083
Lactose Degradation References
Montgomery RK, Buller HA, Rings EH, Grand RJ: Lactose intolerance and the genetic regulation of intestinal lactase-phlorizin hydrolase. FASEB J. 1991 Oct;5(13):2824-32.
Pubmed: 1916106
Mantei N, Villa M, Enzler T, Wacker H, Boll W, James P, Hunziker W, Semenza G: Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme. EMBO J. 1988 Sep;7(9):2705-13.
Pubmed: 2460343
Boll W, Wagner P, Mantei N: Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. Am J Hum Genet. 1991 May;48(5):889-902.
Pubmed: 1902057
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Hediger MA, Turk E, Wright EM: Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5748-52. doi: 10.1073/pnas.86.15.5748.
Pubmed: 2490366
Turk E, Martin MG, Wright EM: Structure of the human Na+/glucose cotransporter gene SGLT1. J Biol Chem. 1994 May 27;269(21):15204-9.
Pubmed: 8195156
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. doi: 10.1186/gb-2004-5-10-r84. Epub 2004 Sep 30.
Pubmed: 15461802
Kawakami K, Ohta T, Nojima H, Nagano K: Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J Biochem. 1986 Aug;100(2):389-97. doi: 10.1093/oxfordjournals.jbchem.a121726.
Pubmed: 2430951
Ruiz A, Bhat SP, Bok D: Characterization and quantification of full-length and truncated Na,K-ATPase alpha 1 and beta 1 RNA transcripts expressed in human retinal pigment epithelium. Gene. 1995 Apr 3;155(2):179-84. doi: 10.1016/0378-1119(94)00812-7.
Pubmed: 7536695
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J, Hoefnagels WA, Black DF, Sandkuijl LA, Frants RR, Ferrari MD, van den Maagdenberg AM: Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol. 2003 Sep;54(3):360-6. doi: 10.1002/ana.10674.
Pubmed: 12953268
De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, Ballabio A, Aridon P, Casari G: Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003 Feb;33(2):192-6. doi: 10.1038/ng1081. Epub 2003 Jan 21.
Pubmed: 12539047
Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart MB, Ptacek LJ, Silver K, Youroukos S: Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Ann Neurol. 2004 Jun;55(6):884-7. doi: 10.1002/ana.20134.
Pubmed: 15174025
Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E, Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L, Huff C, Jorde LB, Reyna SP, Murphy KJ, Shianna KV, Gumbs CE, Little L, Silver K, Ptacek LJ, Haan J, Ferrari MD, Bye AM, Herkes GK, Whitelaw CM, Webb D, Lynch BJ, Uldall P, King MD, Scheffer IE, Neri G, Arzimanoglou A, van den Maagdenberg AM, Sisodiya SM, Mikati MA, Goldstein DB: De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012 Sep;44(9):1030-4. doi: 10.1038/ng.2358. Epub 2012 Jul 29.
Pubmed: 22842232
Ishii A, Saito Y, Mitsui J, Ishiura H, Yoshimura J, Arai H, Yamashita S, Kimura S, Oguni H, Morishita S, Tsuji S, Sasaki M, Hirose S: Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. PLoS One. 2013;8(2):e56120. doi: 10.1371/journal.pone.0056120. Epub 2013 Feb 8.
Pubmed: 23409136
Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM: A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014 Jan 28;9:15. doi: 10.1186/1750-1172-9-15.
Pubmed: 24468074
Keryanov S, Gardner KL: Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4. Gene. 2002 Jun 12;292(1-2):151-66. doi: 10.1016/s0378-1119(02)00647-9.
Pubmed: 12119109
Hlivko JT, Chakraborty S, Hlivko TJ, Sengupta A, James PF: The human Na,K-ATPase alpha 4 isoform is a ouabain-sensitive alpha isoform that is expressed in sperm. Mol Reprod Dev. 2006 Jan;73(1):101-15. doi: 10.1002/mrd.20383.
Pubmed: 16175638
Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. doi: 10.1038/nature04727.
Pubmed: 16710414
Kawakami K, Nojima H, Ohta T, Nagano K: Molecular cloning and sequence analysis of human Na,K-ATPase beta-subunit. Nucleic Acids Res. 1986 Apr 11;14(7):2833-44. doi: 10.1093/nar/14.7.2833.
Pubmed: 3008098
Lane LK, Shull MM, Whitmer KR, Lingrel JB: Characterization of two genes for the human Na,K-ATPase beta subunit. Genomics. 1989 Oct;5(3):445-53.
Pubmed: 2559024
Hernando N, Martin-Vasallo P, Ghosh S, Ghosh PK, Swaroop A, Coca-Prados M: Nucleotide sequence of a cDNA for the beta 2 subunit isoform of Na+,K(+)-ATPase from human retina. Biochim Biophys Acta. 1994 Jan 3;1189(1):109-11. doi: 10.1016/0005-2736(94)90287-9.
Pubmed: 8305453
Ruiz A, Bhat SP, Bok D: Expression and synthesis of the Na,K-ATPase beta 2 subunit in human retinal pigment epithelium. Gene. 1996 Oct 17;176(1-2):237-42. doi: 10.1016/0378-1119(96)00258-2.
Pubmed: 8918259
Avila J, Alvarez de la Rosa D, Gonzalez-Martinez LM, Lecuona E, Martin-Vasallo P: Structure and expression of the human Na,K-ATPase beta 2-subunit gene. Gene. 1998 Feb 27;208(2):221-7. doi: 10.1016/s0378-1119(97)00661-6.
Pubmed: 9524271
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