Structure, biosynthesis and regulation of lactase-phlorizin hydrolase

Abstract

Lactase-phlorizin hydrolase (EC 3.2.1.108; 3.2.1.62) (LPH) is an enterocyte specific enzyme localised to the intestinal brush border. It has a key role in the digestion of lactose. LPH is an ectoenzyme anchored to the microvillar membrane via a C-terminally located hydrophobic stretch and it has an internal homology. LPH is sythesized as a large precursor which during the intracellular transport becomes N- and O- glycosylated. During the transport a large propeptide, which serves as a chaperone, is cleaved off before LPH reaches the brush border. LPH-expression is regulated at the level of LPH-mRNA during both differentiation/tissue specific expression and post-weaning down regulation. A series of regulatory elements together with their transcription factors have been identified. It is suggested that lactase-persistence is caused by a mutation that either destructs a repressive cis-element (or a cis-element binding a destabilising protein) or creates an enhancing cis-element interacting with activating factors which increase after weaning.