View source for Lactase

=== Structure and biosynthesis ===
Preprolactase, the primary translation product, has a single polypeptide primary structure consisting of 1927 amino acids.<ref name="pmid2460343">{{cite journal | vauthors = Mantei N, Villa M, Enzler T, Wacker H, Boll W, James P, Hunziker W, Semenza G | title = Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme | journal = The EMBO Journal | volume = 7 | issue = 9 | pages = 2705–13 | date = Sep 1988 | pmid = 2460343 | pmc = 457059 | doi = 10.1002/j.1460-2075.1988.tb03124.x}}</ref> It can be divided into five domains: (i) a 19-amino-acid cleaved [[Signal peptide|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.<ref name = "pmid2460343"/> 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.<ref>{{cite journal | vauthors = Naim HY, Sterchi EE, Lentze MJ | title = Biosynthesis and maturation of lactase-phlorizin hydrolase in the human small intestinal epithelial cells | journal = The Biochemical Journal | volume = 241 | issue = 2 | pages = 427–34 | date = Jan 1987 | pmid = 3109375 | pmc = 1147578 | doi=10.1042/bj2410427}}</ref> 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.<ref>{{cite journal | vauthors = Naim HY, Jacob R, Naim H, Sambrook JF, Gething MJ | title = The pro region of human intestinal lactase-phlorizin hydrolase | journal = The Journal of Biological Chemistry | volume = 269 | issue = 43 | pages = 26933–43 | date = Oct 1994 | doi = 10.1016/S0021-9258(18)47109-8 | pmid = 7523415 | doi-access = free }}</ref>

[[Image:Lactase Processing.png|500px|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.<ref name = "pmid2460343"/> 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.<ref>{{cite journal | vauthors = Zecca L, Mesonero JE, Stutz A, Poirée JC, Giudicelli J, Cursio R, Gloor SM, Semenza G | title = Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro-LPH maturation | journal = FEBS Letters | volume = 435 | issue = 2–3 | pages = 225–8 | date = Sep 1998 | pmid = 9762914 | doi = 10.1016/S0014-5793(98)01076-X | s2cid = 33421778 | doi-access = free | bibcode = 1998FEBSL.435..225Z }}</ref>