Lactase - wikipedia Lactase Lactase Lactase tetramer, E. Coli Identifiers EC number 3.2. 1.108 CAS number 9031 - 11 - 2 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / QuickGO Search PMC articles PubMed articles NCBI proteins Glycosylceramidase ( Phlorizin hydrolase ) Identifiers EC number 3.2. 1.62 CAS number 9033 - 10 - 7 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / QuickGO Search PMC articles PubMed articles NCBI proteins Lactase Identifiers Symbol LCT Alt. symbols LAC ; LPH ; LPH1 Entrez 3938 HUGO 6530 OMIM 603202 RefSeq NM_002299 UniProt P09848 Other data EC number 3.2. 1.108 Locus Chr. 2 q21 Lactase is an enzyme produced by many organisms. It is located in the brush border of the small intestine of humans and other mammals. Lactase is essential to the complete digestion of whole milk ; it breaks down lactose, a sugar which gives milk its sweetness. Lacking lactase, a person consuming dairy products may experience the symptoms of lactose intolerance. Lactase can be purchased as a food supplement, and is added to milk to produce `` lactose - free '' milk products. Lactase ( also known as lactase - phlorizin hydrolase, or LPH ), a part of the β - galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers. Lactase is present predominantly along the brush border membrane of the differentiated enterocytes lining the villi of the small intestine. In humans, lactase is encoded by the LCT gene. Contents 1 Uses 1.1 Medical use 1.2 Industrial use 2 Mechanism 3 Structure and biosynthesis 4 Genetic expression and regulation 5 See also 6 References 7 External links Uses Medical use Lactase supplements are sometimes used to treat lactose intolerance. Industrial use Lactase produced commercially can be extracted both from yeasts such as Kluyveromyces fragilis and Kluyveromyces lactis and from molds, such as Aspergillus niger and Aspergillus oryzae. Its primary commercial use, in supplements such as Lacteeze and Lactaid, is to break down lactose in milk to make it suitable for people with lactose intolerance, However, the U.S. Food and Drug Administration has not formally evaluated the effectiveness of these products. Lactase is also used to screen for blue white colonies in the multiple cloning sites of various plasmid vectors in Escherichia coli or other bacteria. Mechanism The optimum temperature for human lactase is about 37 ° C for its activity and has an optimum pH of 6. In metabolism, the β - glycosidic bond in D - lactose is hydrolyzed to form D - galactose and D - glucose, which can be absorbed through the intestinal walls and into the bloodstream. The overall reaction that lactase catalyzes is C H O + H O → C H O + C H O + heat. The catalytic mechanism of D - lactose hydrolysis retains the substrate anomeric configuration in the products. While the details of the mechanism are uncertain, the stereochemical retention is achieved through a double displacement reaction. Studies of E. coli lactase have proposed that hydrolysis is initiated when a glutamate nucleophile on the enzyme attacks from the axial side of the galactosyl carbon in the β - glycosidic bond. The removal of the D - glucose leaving group may be facilitated by Mg - dependent acid catalysis. The enzyme is liberated from the α - galactosyl moiety upon equatorial nucleophilic attack by water, which produces D - galactose. Substrate modification studies have demonstrated that the 3 ′ - OH and 2 ′ - OH moieties on the galactopyranose ring are essential for enzymatic recognition and hydrolysis. The 3 ′ - hydroxy group is involved in initial binding to the substrate while the 2 ′ - group is not necessary for recognition but needed in subsequent steps. This is demonstrated by the fact that a 2 - deoxy analog is an effective competitive inhibitor ( K = 10mM ). Elimination of specific hydroxyl groups on the glucopyranose moiety does not completely eliminate catalysis. Lactase also catalyzes the conversion of phlorizin to phloretin and glucose. Structure and biosynthesis Preprolactase, the primary translation product, has a single polypeptide primary structure consisting of 1927 amino acids. It can be divided into five domains : ( i ) a 19 - amino - acid cleaved signal sequence ; ( ii ) a large prosequence domain that is not present in mature lactase ; ( iii ) the mature lactase segment ; ( iv ) a membrane - spanning hydrophobic anchor ; and ( v ) a short hydrophilic carboxyl terminus. The signal sequence is cleaved in the endoplasmic reticulum, and the resulting 215 - kDa pro-LPH is sent to the Golgi apparatus, where it is heavily glycosylated and proteolytically processed to its mature form. The prodomain has been shown to act as an intramolecular chaperone in the ER, preventing trypsin cleavage and allowing LPH to adopt the necessary 3 - D structure to be transported to the Golgi apparatus. Schematic of processing and localization of human lactase translational product Mature human lactase consists of a single 160 - kDa polypeptide chain that localizes to the brush border membrane of intestinal epithelial cells. It is oriented with the N - terminus outside the cell and the C - terminus in the cytosol. LPH contains two catalytic glutamic acid sites. In the human enzyme, the lactase activity has been connected to Glu - 1749, while Glu - 1273 is the site of phlorizin hydrolase function. Genetic expression and regulation Lactase is encoded by a single genetic locus on chromosome 2. It is expressed exclusively by mammalian small intestine enterocytes and in very low levels in the colon during fetal development. Humans are born with high levels of lactase expression. In most of the world 's population, lactase transcription is down - regulated after weaning, resulting in diminished lactase expression in the small intestine, which causes the common symptoms of adult - type hypolactasia, or lactose intolerance. Some population segments exhibit lactase persistence resulting from a mutation that is postulated to have occurred 5,000 -- 10,000 years ago, coinciding with the rise of cattle domestication. This mutation has allowed almost half of the world 's population to metabolize lactose without symptoms. Studies have linked the occurrence of lactase persistence to two different single - nucleotide polymorphisms about 14 and 22 kilobases upstream of the 5 ' - end of the LPH gene. Both mutations, C → T at position - 13910 and G → A at position - 22018, have been independently linked to lactase persistence. The lactase promoter is 150 base pairs long and is located just upstream of the site of transcription initiation. The sequence is highly conserved in mammals, suggesting that critical cis - transcriptional regulators are located nearby. Cdx - 2, HNF - 1α, and GATA have been identified as transcription factors. Studies of hypolactasia onset have demonstrated that despite polymorphisms, little difference exists in lactase expression in infants, showing that the mutations become increasingly relevant during development. Developmentally regulated DNA - binding proteins may down - regulate transcription or destabilize mRNA transcripts, causing decreased LPH expression after weaning. See also Molecular and Cellular Biology portal MCM6 Lactase persistence References Jump up ^ Järvelä I, Torniainen S, Kolho KL ( 2009 ). `` Molecular genetics of human lactase deficiencies ''. Annals of Medicine. 41 ( 8 ) : 568 -- 75. doi : 10.1080 / 07853890903121033. PMID 19639477. ^ Jump up to : Skovbjerg H, Sjöström H, Norén O ( Mar 1981 ). `` Purification and characterisation of amphiphilic lactase / phlorizin hydrolase from human small intestine ''. European Journal of Biochemistry / FEBS. 114 ( 3 ) : 653 -- 61. doi : 10.1111 / j. 1432 - 1033.1981. tb05193. x. PMID 6786877. ^ Jump up to : Mantei N, Villa M, Enzler T, Wacker H, Boll W, James P, Hunziker W, Semenza G ( Sep 1988 ). `` Complete primary structure of human and rabbit lactase - phlorizin hydrolase : implications for biosynthesis, membrane anchoring and evolution of the enzyme ''. The EMBO Journal. 7 ( 9 ) : 2705 -- 13. PMC 457059. PMID 2460343. Jump up ^ Harvey CB, Fox MF, Jeggo PA, Mantei N, Povey S, Swallow DM ( Jul 1993 ). `` Regional localization of the lactase - phlorizin hydrolase gene, LCT, to chromosome 2q21 ''. Annals of Human Genetics. 57 ( Pt 3 ) : 179 -- 85. doi : 10.1111 / j. 1469 - 1809.1993. tb01593. x. PMID 8257087. Jump up ^ `` Lactose Intolerance ''. NIDDK. June 2014. Retrieved 25 October 2016. Jump up ^ Seyis I, Aksoz N ( 2004 ). `` Production of lactase by Trichoderma sp '' ( PDF ). Food Technol Biotechnol. 42 : 121 -- 124. Jump up ^ `` Re : GRAS Notification for Acid Lactase from Aspergillus oryzae Expressed in Aspergillus niger ''. United States Food and Drug Administration. Jump up ^ Holsinger VH. `` The Lactaid Story ''. Innovative Products for Food Industries. pp. 256 -- 8. Jump up ^ Tarantino, LM ( 2003 - 12 - 03 ). `` Agency Response Letter GRAS Notice No. GRN 000132 ''. U.S. Food and Drug Administration. Retrieved 2009 - 09 - 21. Jump up ^ Hermida C, Corrales G, Cañada FJ, Aragón JJ, Fernández - Mayoralas A ( Jul 2007 ). `` Optimizing the enzymatic synthesis of beta - D - galactopyranosyl - D - xyloses for their use in the evaluation of lactase activity in vivo ''. Bioorganic & Medicinal Chemistry. 15 ( 14 ) : 4836 -- 40. doi : 10.1016 / j. bmc. 2007.04. 067. PMID 17512743. ^ Jump up to : Sinnott M ( November 1990 ). `` Catalytic mechanisms of enzymic glycosyl transfer ''. Chem. Rev. 90 ( 7 ) : 1171 -- 1202. doi : 10.1021 / cr00105a006. ^ Jump up to : Juers DH, Heightman TD, Vasella A, McCarter JD, Mackenzie L, Withers SG, Matthews BW ( Dec 2001 ). `` A structural view of the action of Escherichia coli ( lacZ ) beta - galactosidase ''. Biochemistry. 40 ( 49 ) : 14781 -- 94. doi : 10.1021 / bi011727i. PMID 11732897. ^ Jump up to : Fernandez P, Cañada FJ, Jiménez - Barbero J, Martín - Lomas M ( Jul 1995 ). `` Substrate specificity of small - intestinal lactase : study of the steric effects and hydrogen bonds involved in enzyme - substrate interaction ''. Carbohydrate Research. 271 ( 1 ) : 31 -- 42. doi : 10.1016 / 0008 - 6215 ( 95 ) 00034 - Q. PMID 7648581. Jump up ^ Naim HY, Sterchi EE, Lentze MJ ( Jan 1987 ). `` Biosynthesis and maturation of lactase - phlorizin hydrolase in the human small intestinal epithelial cells ''. The Biochemical Journal. 241 ( 2 ) : 427 -- 34. doi : 10.1042 / bj2410427. PMC 1147578. PMID 3109375. Jump up ^ Naim HY, Jacob R, Naim H, Sambrook JF, Gething MJ ( Oct 1994 ). `` The pro region of human intestinal lactase - phlorizin hydrolase ''. The Journal of Biological Chemistry. 269 ( 43 ) : 26933 -- 43. PMID 7523415. Jump up ^ Zecca L, Mesonero JE, Stutz A, Poirée JC, Giudicelli J, Cursio R, Gloor SM, Semenza G ( Sep 1998 ). `` Intestinal lactase - phlorizin hydrolase ( LPH ) : the two catalytic sites ; the role of the pancreas in pro-LPH maturation ''. FEBS Letters. 435 ( 2 - 3 ) : 225 -- 8. doi : 10.1016 / S0014 - 5793 ( 98 ) 01076 - X. PMID 9762914. ^ Jump up to : Troelsen JT, Mitchelmore C, Spodsberg N, Jensen AM, Norén O, Sjöström H ( Mar 1997 ). `` Regulation of lactase - phlorizin hydrolase gene expression by the caudal - related homoeodomain protein Cdx - 2 ''. The Biochemical Journal. 322 ( Pt 3 ) ( Pt. 3 ) : 833 -- 8. PMC 1218263. PMID 9148757. Jump up ^ https://ghr.nlm.nih.gov/gene/LCT Jump up ^ Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN ( Jun 2004 ). `` Genetic signatures of strong recent positive selection at the lactase gene ''. American Journal of Human Genetics. 74 ( 6 ) : 1111 -- 20. doi : 10.1086 / 421051. PMC 1182075. PMID 15114531. Jump up ^ Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A, Järvelä I ( May 2003 ). `` Transcriptional regulation of the lactase - phlorizin hydrolase gene by polymorphisms associated with adult - type hypolactasia ''. Gut. 52 ( 5 ) : 647 -- 52. doi : 10.1136 / gut. 52.5. 647. PMC 1773659. PMID 12692047. ^ Jump up to : Troelsen JT ( May 2005 ). `` Adult - type hypolactasia and regulation of lactase expression ''. Biochimica et Biophysica Acta. 1723 ( 1 - 3 ) : 19 -- 32. doi : 10.1016 / j. bbagen. 2005.02. 003. PMID 15777735. ^ Jump up to : Wang Y, Harvey CB, Hollox EJ, Phillips AD, Poulter M, Clay P, Walker - Smith JA, Swallow DM ( Jun 1998 ). `` The genetically programmed down - regulation of lactase in children ''. Gastroenterology. 114 ( 6 ) : 1230 -- 6. doi : 10.1016 / S0016 - 5085 ( 98 ) 70429 - 9. PMID 9609760. External links Wikimedia Commons has media related to Lactase. The Lactase Protein E. coli β - galactosidase : PDB : 1JYY ​ Gene Ontology for Lactase Making of the Fittest : Got Lactase ? The Co-evolution of Genes and Culture Lactase persistence shows indication of association with Obesity Metabolism : carbohydrate metabolism fructose and galactose enzymes Fructose / Fructolysis Hepatic fructokinase Aldolase B Triokinase Sorbitol Sorbitol dehydrogenase Aldose reductase Galactose / Galactolysis Galactokinase Galactose - 1 - phosphate uridylyltransferase / UDP - glucose 4 - epimerase Aldose reductase Lactose Lactose synthase Lactase Mannose Mannose phosphate isomerase Hydrolase : sugar hydrolases ( EC 3.2 ) 3.2. 1 : Glycoside hydrolases Disaccharidase Sucrase / Sucrase - isomaltase / Invertase Maltase Trehalase Lactase Glucosidases Cellulase Alpha - glucosidase Acid Neutral AB Neutral C Beta - glucosidase cytosolic Debranching enzyme Other Amylase Alpha - amylase Chitinase Lysozyme Neuraminidase NEU1 NEU2 NEU3 NEU4 Bacterial neuraminidase Viral neuraminidase Galactosidases Alpha Beta alpha - Mannosidase Glucuronidase Hyaluronidase Pullulanase Glucosylceramidase lysosomal non-lysosomal Galactosylceramidase Alpha - N - acetylgalactosaminidase NAGA Alpha - N - acetylglucosaminidase Fucosidase Hexosaminidase HEXA HEXB Iduronidase Maltase - glucoamylase Heparanase HPSE2 3.2. 2 : Hydrolysing N - Glycosyl compounds DNA glycosylases : Oxoguanine glycosylase Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie -- Hofstee diagram Hanes -- Woolf plot Lineweaver -- Burk plot Michaelis -- Menten kinetics Types EC1 Oxidoreductases ( list ) EC2 Transferases ( list ) EC3 Hydrolases ( list ) EC4 Lyases ( list ) EC5 Isomerases ( list ) EC6 Ligases ( list ) Retrieved from `` https://en.wikipedia.org/w/index.php?title=Lactase&oldid=806704324 '' Categories : Genes on human chromosome 2 Food additives Antiflatulents EC 3.2. 1 Hidden categories : Protein pages needing a picture All articles with unsourced statements Articles with unsourced statements from April 2010 Talk Search Contents About Wikipedia বাংলা Català Čeština Dansk Deutsch Ελληνικά Español Esperanto Euskara فارسی Français Galego 한국어 Hrvatski Ido Íslenska Italiano עברית Magyar Nederlands 日本 語 Occitan Oʻzbekcha / ўзбекча Polski Português Русский Simple English Slovenčina Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Tagalog Українська 粵語 中文 Edit links This page was last edited on 23 October 2017, at 17 : 10. 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Question: where is lactase produced in the digestive system
Answer: brush border of the small intestine