| http://biocyc.org/biopax/bi... | biopax3:comment | The native relative molecular mass of lactase (lactase-phlorizin hydrolase) was determined by gel filtration chromatography |CITS: [6786877]|. Lactase (lactase/phlorizin hydrolase, LPH) hydrolyzes lactose, the major carbohydrate in milk. It is a critical enzyme during the mammalian neonatal period. Lactose must be hydrolyzed to galactose and glucose to be absorbed in the intestine. It is expressed developmentally and regulated at the transcriptional level. A deficiency or absence of lactase is associated with lactose intolerance, a common intestinal disorder. A rare congenital form of lactose intolerance also exists (reviewed in |CITS: [11332711] [1916106]|, in |CITS: [11106409]|). The mammalian enzyme also hydrolyzes |FRAME: CPD-12447|, a naturally occurring dihydrochalcone found in fruit trees that is a pharmaceutical research tool and potential drug (reviewed in |CITS: [15624123]|). It also hydrolyzes glycosylceramides. The broad substrate specificity of this mammalian enzyme has been described by EC 3.2.1.108, EC 3.2.1.62 and EC 3.2.1.23. It has been referred to as the lactase/phlorizin hydrolase complex, EC 3.2.1.108/62 |CITS: [11106409]|, or earlier EC 3.2.1.23/62 |CITS: [6786877]| and reviewed in |CITS: [1916106]|. However, a difference in substrate specificity between human lactase and human β-galactosidase from small intestine has been demonstrated. Also see the summary in MetaCyc pathway |FRAME: BGALACT-PWY|. Human small intestinal lactase is located in the brush-border epithelial cell membrane. It is synthesized as a large, single-chain prepro-LPH containing four homologous regions, I-IV, derived from internal gene duplication. Prepro-LPH is cleaved to a 215 kDa pro-LPH in the endoplasmic reticulum and then cleaved to a 160 kDa LPH polypeptide after terminal glycosylation in the Golgi apparatus. In the brush-border membrane, luminal trypsin creates an additional cleavage which produces the physiologically active enzyme (in |CITS: [11751874] [11106409]| and reviewed in |CITS: [1916106]|). The 160 kDa human enzyme was shown to be a homodimer |CITS: [8832204]| with two distinct active sites (|CITS: [11106409]| and reviewed in |CITS: [1916106]|). The mature LPH polypeptide contains regions III and IV, each homologous to family 1 glycosidases. This amphiphilic molecule also contains a transmembrane segment and a cytoplasmic C-terminus. The active site for lactase activity is in region IV, and phlorizin hydrolysis occurs mainly at the active site in region III |CITS: [11106409] [9762914]| . These assignments are in contrast to earlier affinity labeling studies |CITS: [1388157]|. The physiological function of the phlorizin hydrolase active site is unknown, but it is hypothesized to have glycosylceramidase activity (EC 3.2.1.62) (in |CITS: [11106409]|). Glycosylceramidase activity has been shown for the rat, monkey and mouse enzymes |CITS: [4752949] [810166] [2508486] [6790523]|. The human enzyme has been reported to use glycolipids as a substrate <i>in vitro</i> (reviewed in |CITS: [1916106]|). | lld:biopax3 |
