Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human lactase-phlorizin hydrolase (EC 3.2.1.23/62) is a major disaccharidase in the microvillus membrane of small intestinal epithelial cells. The enzyme is synthesized as a single-chain precursor protein and undergoes proteolytic processing during maturation. We studied proteolytic processing of human lactase-phlorizin hydrolase in transfected COS-1, Caco-2, and MDCK cells using metabolic labeling, surface immunoprecipitation, protease sensitivity assays, and microsequencing. Furthermore, we generated mutated forms of the enzyme to alter potential proteolytic cleavage sites and expressed these in Caco-2 and COS-1 cells. Since the N-terminal amino acid of microvillus lactase-phlorizin hydrolase corresponds to Ala869 in the precursor protein, it has been speculated that processing occurs at position Arg868-Ala869. Substitution of Arg868 with isoleucine, lysine, or glutamic acid had no effect on the proteolytic processing of pro-LPH in Caco-2 cells. As in wild-type enzyme a processed 160-kDa form was generated. These data are not consistent with a primary proteolytic processing at position Arg868-Ala869. Using amino-terminal amino acid sequencing of this processed form isolated from stable transfected MDCK cells we identified the cleavage site at Arg734-Leu735. Treatment of pro-lactase-phlorizin hydrolase expressed in COS-1 and MDCK cells by trypsin yielded a 145-kDa form with an identical amino terminal as the mature microvillus enzyme isolated from intestinal mucosa (Ala869). These data provide unambiguous evidence of a two-step processing of human lactase-phlorizin hydrolase. The first cleavage occurs intracellularly after a dibasic site (Arg734-Leu735) and yields the 160-kDa intermediate form. In a second step the intermediate form inserted into the microvillus membrane is trimmed to the mature enzyme by luminal trypsin.
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PMID:Proteolytic processing of human lactase-phlorizin hydrolase is a two-step event: identification of the cleavage sites. 895 Oct 31

This prospective cross-sectional study aimed to investigate the potential association between primary-adult lactose malabsorption, fructose malabsorption, tryptophan (TRP) metabolism and the presence of depressive signs. Overall 251 patients, who were referred for lactase gene C/T-13910 polymorphism genotyping and fructose hydrogen/methane breath testing, were included. All participants filled out the Beck Depression Inventory (BDI II). Serum concentrations of tryptophan (TRP), kynurenine (KYN), kynuric acid (KYNA), and TRP competing amino acids (leucine, isoleucine, valine, phenylalanine, tyrosine) were measured by high-pressure liquid-chromatography. Logistic regression analysis was performed with lactose malabsorption, fructose malabsorption and all potential biomarkers of TRP metabolism to assess the effect on signs of depression, defined as a BDI II score > 13. Primary-adult lactose malabsorption and fructose malabsorption was detected in 65 (25.90%) and 65 (25.90%) patients, respectively. Fructose malabsorption was significantly associated with BDI II score, whereas no such relationship was found for lactose malabsorption. Serum levels of TRP and TRP metabolites were no predictors of depression. The authors suggest to conduct further prospective longitudinal studies in order to get further insight of associations between carbohydrate malabsorption, biomarkers and mood disorders.
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PMID:Assessment of tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption. 2896 10