Disease relevance of Cel

• Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension [1].
• BAL (50 mg/kg) alone or in combination with DTPA (50 mg/kg) was effective in removing cadmium from the body without increasing the level of cadmium in the kidney, the critical organ in cadmium toxicity [2].
• DESIGN: The density of inflammatory cells in BAL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis [3].
• We have also measured the acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol-esterase (CEH) activity during endotoxic shock [4].
• 1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol) [5].

High impact information on Cel

• Experiments performed in vivo with hypophysectomized female rats indicate that the trypsin digest of 16k fragment stimulates cholesterol ester hydrolase (cholesterol esterase; sterol-ester acylhydrolase, EC 3.1.1.13) activity in the adrenal cortex but fails to activate cholesterol side-chain cleavage [6].
• In contrast, the R63A and R423A mutant enzymes displayed 5- and 11-fold decreases in k(cat), in comparison with wild type CEL, for bile salt-dependent cholesteryl ester hydrolysis [7].
• However, the x-ray crystal structure of CEL failed to show the involvement of arginine residues in CEL-bile salt interaction [7].
• Although taurocholate induced similar changes in circular dichroism spectra for wild type, R63A, and R423G proteins, this bile salt was less efficient in protecting the mutant enzymes against thermal inactivation in comparison with control CEL [7].
• Mutations of Arg(63) to Ala(63) (R63A) and Arg(423) to Gly(423) (R423G) resulted in enzymes with increased bile salt-independent hydrolytic activity against lysophosphatidylcholine, having 6.5- and 2-fold higher k(cat) values, respectively, in comparison to wild type CEL [7].

Chemical compound and disease context of Cel

• These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane [1].
• Aortic cholesterol esterase and other lysosomal enzyme activities in DOCA-salt, renal and spontaneous hypertension in the rat [8].
• For clinical practice, DMSA and DMPS may well be the chelators of choice; the application of BAL should be reserved for very severe cases of poisoning because of its own toxicity [9].
• 2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits [5].
• BAL 31 digestion of fragment II showed that the sequence element that was responsible for the increased association with nuclear matrix proteins during the acute phase response was a tract of 38 adenine bases [10].

Biological context of Cel

• Identification of the active site serine in pancreatic cholesterol esterase by chemical modification and site-specific mutagenesis [11].
• Based on this sequence homology, it was hypothesized that histidine 435 is the histidine residue essential for catalytic activity of cholesterol esterase [12].
• These studies definitively identified serine 194 in the catalytic site of pancreatic cholesterol esterase [11].
• In contrast, mutagenesis of the histidine residue at position 420 to glutamine had no effect on cholesterol esterase enzyme activity [12].
• Analysis of overlapping genomic clones showed that the cholesterol esterase gene spans approximately 8 kb, containing 11 exons interrupted by 10 introns [13].

Anatomical context of Cel

• On the other hand, cholesterol esterase activity (expressed either pmol.min-1.CL-1 or pmol.min-1.mg protein-1) was similar in all three groups and comparable to corpora lutea from intact pregnant rats [14].
• Arterial wall lipase and cholesterol esterase were associated with both the lysosome and microsome fractions, whereas acyl CoA synthetase, triglyceride synthesizing activity, cholesteryl ester synthesizing activity and cytidine diphosphatecholine-1,2-diacyl glycerol choline phosphotransferase (CPT) were found mainly in the microsomal fraction [15].
• Northern blot hybridization showed that the bile salt-stimulated cholesterol esterase mRNA is present in liver suggesting that this protein may also be synthesized by liver cells [16].
• Expression of the cDNA in COS cells resulted in the production of bile salt-stimulated cholesterol esterase [16].
• Whole blood and ultrafiltrate conductivity in the portal vein (as a measure of hematocrit and total electrolyte concentration, Cel, respectively) and arterial pressure of alert rats were measured continuously [17].

Associations of Cel with chemical compounds

• Substitution of the histidine in position 435 with glutamine, arginine, alanine, serine, or aspartic acid abolished the ability of cholesterol esterase to hydrolyze p-nitrophenyl butyrate and cholesterol [14C]oleate [12].
• Site-specific mutagenesis of an essential histidine residue in pancreatic cholesterol esterase [12].
• The codon for serine 194 in rat cholesterol esterase cDNA was then mutagenized to ACT or GCT to yield mutagenized cholesterol esterase with either threonine or alanine, instead of serine, at position 194 [11].
• In the first approach, purified porcine pancreatic cholesterol esterase was covalently modified by incubation with [3H]diisopropylfluorophosphate (DFP) [11].
• Analysis of the cholesterol esterase structure also revealed a repetitive sequence enriched with Pro, Asp, Glu, Ser, and Thr residues at the C-terminal end of the protein [16].

Regulatory relationships of Cel

• The synthesis and secretion of cholesterol esterase were stimulated 2-5-fold by incubating the cells with 0.5-4 nM of cholecystokinin or 0.5-2 nM of secretin [18].
• Amylin dose-dependently stimulated the secretion of amylase and cholesterol esterase from rat pancreatic acinar AR42J cells [19].

Other interactions of Cel

• In the first approach, comparison of the primary structure of rat pancreatic cholesterol esterase with that of acetylcholinesterase and cholinesterase revealed two conserved histidine residues located at positions 420 and 435 [12].
• The results of this study strongly suggested that histidine 435 may be a component of the catalytic triad of pancreatic cholesterol esterase [12].
• Linkage mapping of the carboxyl ester lipase gene (Cel) to rat chromosome 3 [20].
• To assess the role of each enzyme, [4-14C]cholesterol absorption into mesenteric lymph of rats with normal mucosal levels of both esterification enzymes was compared with that of rats with normal acyl coenzyme A:cholesterol acyltransferase activity but deficient cholesterol esterase activity [21].
• The coordinated regulation of cholesterol esterase with another lipid digestive enzyme, the pancreatic lipase, suggested an important role for these proteins in dietary lipid absorption through the gastrointestinal tract [22].

Analytical, diagnostic and therapeutic context of Cel

• The role of His435 in the catalytic activity of pancreatic cholesterol esterase was then studied by the site-specific mutagenesis technique [12].
• The radiolabeled cholesterol esterase was digested with CNBr, and the peptides were separated by high performance liquid chromatography [11].
• Molecular cloning and expression of cDNA for rat pancreatic cholesterol esterase [16].
• This article, which expands on our previous work (Mol. Cel. Biol., 2003), directly compares GCMS- and NMR-determined 13C-isotopomer and flux data obtained from ex vivo rat heart perfusion studies with 13C-substrates [23].
• In contrast, cholesterol esterase activity in rat intestinal mucosa was unaffected by either the induction of diabetes or the atherogenic diet feeding [24].

References