Disease relevance of PNLIP

• During the last few years, a number of protein structures (15-lipoxygenase, alpha-toxin from Clostridium perfringens) have been determined that contain domains with close structural homologies with the beta-sandwich C-terminal domain of PL [1].
• Colipase and maximally activated pancreatic lipase in normal subjects and patients with steatorrhea [2].
• Immunoreactive pancreatic lipase test for neonatal detection of cystic fibrosis [3].
• Excellent correlation was found in normal subjects and patients with pancreatic disease (r = 0.89) between lipase output in the duodenum and the 6-h cumulative 13CO2 excretion in breath, indicating that the mixed triglyceride breath test is an excellent noninvasive test of pancreatic lipase activity in the duodenum [4].
• Patients with exocrine pancreatic insufficiency may absorb greater than 50% of dietary fat despite the absence of measurable pancreatic lipase activity [5].

Psychiatry related information on PNLIP

• The effect of hashish-smoking on serum levels of pancreatic lipase (EC 3.1.1.3) in man [6].

High impact information on PNLIP

• Determination of the three-dimensional structure of pancreatic lipase has revealed the presence of two domains: an amino-terminal domain, at residues 1-336 containing the active site and a carboxy-terminal domain at residues 337-449 (ref. 6). Procolipase binds exclusively to the C-terminal domain of lipase [7].
• Pancreatic lipase (triacylglycerol acyl hydrolase) fulfills a key function in dietary fat absorption by hydrolysing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids [8].
• Under simulated physiological conditions, hydrolysis of emulsified fat droplets by human pancreatic lipase in the presence of colipase and bile salt micelles proceeds with the sequential formation of two visible product phases [9].
• Human milk fat globules require colipase to be hydrolyzed by pancreatic lipase in the presence of bile salts [10].
• At pH 8.0 in 4 mM sodium taurodeoxycholate, lipase activity was due to pancreatic lipase in samples from normal and steatorrheic individuals and was proportional to the concentration of endogenous colipase in samples that could be activated by exogenous colipase [2].

Chemical compound and disease context of PNLIP

• The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications [11].
• While Pseudomonas sp. and human pancreatic lipase are inhibited by tetrahydrolipstatin (THL), the lipase from Candida rugosa is not [12].
• Immunochemical qualitative latex agglutination test for pancreatic lipase in serum evaluated for use in diagnosis of acute pancreatitis [13].
• Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy [14].
• Pluronic F-68, a hydrophilic surface-active agent which was a poor in-vitro inhibitor of human pancreatic lipase, did not produce decreases in body-weight gain or increase fecal-fat excretion in rats [15].

Biological context of PNLIP

• Incubation of RP-containing emulsions with horse PL and colipase resulted in RP hydrolysis (0.051+/-0.01 mumol/min/mg) [16].
• The two novel proteins show an amino acid sequence identity to hPL of 68 and 65% for hPLRP1 and 2, respectively [17].
• Reactivation of the totally inactive pancreatic lipase RP1 by structure-predicted point mutations [18].
• An amino-acid substitution (Ala 178 Val) in the DPLRP1 may result in a steric clash with one of the acyl chains observed in the structures of a C11 alkyl phosphonate inhibitor, a transition state analogue, bound to the classical PL [18].
• These associations were most likely due to linkage disequilibrium with another functional variant at or near PNLIP [19].

Anatomical context of PNLIP

• Both classical pancreatic lipase (DPL) and pancreatic lipase-related protein 1 (DPLRP1) have been found to be secreted by dog exocrine pancreas [18].
• Discoordinate expression of pancreatic lipase and two related proteins in the human fetal pancreas [20].
• Southern blot analysis, using a pancreatic lipase cDNA to probe DNA from mouse-human somatic cell hybrids, indicated that the pancreatic lipase gene (PNLIP) resides on human chromosome 10 [21].
• Preparation and characterization of reference materials for human pancreatic lipase: BCR 693 (from human pancreatic juice) and BCR 694 (recombinant) [22].
• Mixed triglyceride breath test: a noninvasive test of pancreatic lipase activity in the duodenum [4].

Associations of PNLIP with chemical compounds

• Pure horse PL, horse PLRP2 and dog PLRP1 were incubated with RP solubilized in its physiological vehicles, i.e., triglyceride-rich lipid droplets, mixed micelles and vesicles [16].
• Pancreatic lipase and pancreatic lipase-related protein 2, but not pancreatic lipase-related protein 1, hydrolyze retinyl palmitate in physiological conditions [16].
• The predicted NH2-terminal protein sequence agreed with the published NH2-terminal sequence of human pancreatic lipase and the predicted protein sequence was 85 and 70% identical to the protein sequences of pig and dog pancreatic lipase, respectively [23].
• Using rabbit pancreatic lipase, we found that deoxycholate enhanced dioleoylglycerol hydrolysis to a higher degree than trioleoylglycerol hydrolysis [24].
• Recombinant human pancreatic lipase was expressed in broth cultures and was purified from the medium by DEAE blue Sepharose and hydroxyapatite chromatography [25].

Enzymatic interactions of PNLIP

• PLRP2 hydrolyzed RP solubilized in micelles but less efficiently than PL (0.023+/-0.005 mumol/min/mg) [16].
• The bile salt-stimulated lipase also catalyzed incorporation of fatty acids into acylglycerols to a much lesser extent than did pancreatic lipase [26].

Regulatory relationships of PNLIP

• Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release [27].
• Gastric lipase was totally inhibited by 40 mg AR25/g tributyrin whereas pancreatic lipase inhibition was maximum (78.8 +/- 0.7%) with 80 mg AR25/g tributyrin [28].

Other interactions of PNLIP

• Both PL and PLRP2 hydrolyzed RP solubilized in a vesicle rich-solution, and a synergic phenomenon between the two lipases was enlighten [16].
• The protein encoded by the pancreatic colipase (CLPS) gene is an essential cofactor needed by pancreatic triglyceride lipase (PNLIP) for efficient dietary lipid hydrolysis [29].
• Human hepatic lipase and lipoprotein lipase share extensive homology with pancreatic lipase, suggesting that the three proteins are members of a small gene family [23].
• An Alu sequence is conserved in the homologous introns of hPL and the lipoprotein lipase-encoding gene [30].
• Indirect evidence for this new function of the PL C-terminal domain has been provided by studies with monoclonal antibodies directed against the beta5' loop [1].

Analytical, diagnostic and therapeutic context of PNLIP

• Gastric lipase activity was clearly distinguished from that of pancreatic lipase by using both a specific enzymatic assay and an enzyme-linked immunosorbent assay [31].
• To examine the role of trophoblast differentiation in the expression of the hCG and hPL genes, we studied the cytological distribution of their messenger RNA (mRNA) in tissue sections of human hydatidiform mole and choriocarcinoma by in situ hybridization [32].
• By site-specific mutagenesis of the cDNA for human pancreatic lipase, amino acid substitutions were made at Ser153, His264, and Asp177 [33].
• Both the medium and the cells were examined for the presence of pancreatic lipase by Western blot analysis [33].
• The x-ray crystallography structure of human pancreatic lipase suggests that the analogous serine residue in human pancreatic lipase, Ser152, is the nucleophilic residue essential for catalysis [34].

References