Intestinal lactase‐phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro‐LPH maturation

Abstract

Brush border lactase-phlorizin hydrolase carries two catalytic sites. In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. The proteolytic processing of pro-lactase-phlorizin hydrolase by (rat) enterocytes stops two amino acid residues short of the N-terminus of`mature' final, brush border lactase-phlorizin hydrolase. Only these two amino acid residues are removed by luminal pancreatic protease(s), probably trypsin.z 1998 Federation of European Biochemical Societies.

Processing of Human Intestinal Prolactase to an Intermediate Form by Furin or by a Furin-like Proprotein Convertase

“…. (51). The enterocytes can, therefore, almost (but not quite) produce mature, brush-border LPH in the absence of trypsin.…”

Structural Hierarchy of Regulatory Elements in the Folding and Transport of an Intestinal Multidomain Protein

“…It harbors the lactase catalytic site at Glu 1749 (9,22) and acquires activity only when LPH dimerizes (35). Therefore, domain IV plays a role as a regulatory switch that triggers the dimerization of the LPH molecule, thus activating itself and elevating the phlorizin hydrolase activities in domain III.…”

“…It is devoid of sorting signals and catalytic activity and rich in cysteine and hydrophobic amino acid residues (9). LPH is cleaved in the trans-Golgi network by a trypsin-like protease (10 -13) at Arg 734 /Leu 735 generating LPH␤initial (160 kDa) (14 -16), whereby the profragment LPH␣ is ultimately degraded (17,18).…”

“…The catalytic sites of LPH are localized in homologous domains III and IV (9,22). This has raised the question whether these domains behave as autonomous regions and attain their enzymatically active conformation independently of each other in the context of the folding of the LPH.…”

Infantile Lactase Deficiency and Dietary Habits. Cliunical Cases

“…Активный фермент имеет 2 катали-тических участка. Лактазная активность связана с участ-ком Glu-1749, в то время как активность в отношении флоризина -с участком Glu-1273 [3].…”