Cholesterol ester hydrolase

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

The chemical methods for the quantitation of cholesterol measure total cholesterol, i.e. free and esterified, and so a digitonin precipitate must be prepared if free cholesterol is to be measured. Enzymic methods do not measure the esters and a hydrolysis stage, either chemical or enzymic (using cholesterol ester hydrolase, EC 3.1.1.13), is necessary for the measurement of total cholesterol. 

H. K. Bhat, G. A. S. Ansari, Cholesterol Ester Hydrolase Mediated Conjugation of Ha-loethanols with Fatty Acids , Chem. Res. Toxicol. 1990, 3, 311 -317. 

Cholesteryl ester degradation Most dietary cholesterol is present in the free (nonesterified) form, with ten to fifteen percent present in the esterified form. Cholesteryl esters are hydrolyzed by pancreatic cholesterol ester hydrolase (cholesterol esterase), which produces cholesterol plus free fatty acids (see Figure 15.2). Cholesteryl esteh hydrolase activity is greatly increased in the presence of bile salts. ... 

The release of cholesterol from cholesterol esters occurs extra-mitochondrially by means of a cholesterol ester hydrolase in adrenals, ovaries and testicular Ley dig cells (see Ref. 6 for review). This enzyme has been studied mostly in adrenal preparations, and is known to be activated and de-activated by reversible phosphorylation [14] and that the phosphorylation was brought about by a c-AMP-dependent protein kinase [15]. Hence, ACTH stimulation of cholesterol ester activity in the adrenal occurs via the kinase and, in a similar way, trophic hormone stimulation of ovarian and testicular cholesterol ester hydrolases may occur and provide a large pool of cholesterol for steroidogenesis [16-18],... 

Fig. 3. The rate-limiting step of steroidogenesis under ACTH regulation. The transfer of cholesterol (C) from the outer to the inner mitochondrial membrane under ACTH regulation (step 3) makes cholesterol available to cytochrome /M50scc for conversion to pregnenolone (step 4), which diffuses out of the mitochondrion (step 5). Because of its insolubility in aqueous media, cholesterol must be transported to mitochondria, probably by SCP2, from a precursor pool (step 2). Here, cholesterol in the precursor pool is shown as being formed from cholesterol esters (CE) by cholesterol ester hydrolase (CEH) (step 1) other possible pathways are shown in Figs. 4 and 6. From Ref. 14.

Enzymes. Many enzyme activities have been found in myelin neuraminidase, cholesterol ester hydrolase, lipid synthesizing and catabolizing enzymes, proteases, protein kinases, and phosphatases. Two of them have been especially characterized. 

Dietary triglycerides and esterified cholesterol and phospholipids are broken down in the intestine Uiivugh, respectively, pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2, to form free fatty acids, unesterified cholesterol and lysophospholipids (phospholipids with only one fatty acid group), which are absorbed. 

Reproductive effects of molinate may depend on inhibition of neutral cholesterol ester hydrolase, leading to disruption of mobilization of cholesterol from high-density lipoprotein, a process selective for... 

Pancreatic lipase, in the presence of bile salts and coUpase, acts at the oil-water interface of the triglyceride emulsion to produce fatty acids and 2-monoacylglycerols. Cohpase is secreted in pancreatic juice as an inactive proenzyme, which is converted to the active form by trypsin. Other significant enzymes involved in the breakdown of fats within the intestinal lumen are cholesterol ester hydrolase, phospholipase A, and a nonspecific bile salt-activated lipase. 

Ruble T, Trottmann M, Lorenz RL (2004) Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette Al in monocytoid cells by niacin. Biochem Pharmacol 67 411 19 Sakurada T, Orimo H, Okabe H, et al. (1976) Purification and properties of cholesterol ester hydrolase from... 

ADP AFP ab as ALAT AP ASAT ATP BQ BSA CEH CK CME COD con A CV d D E E EC ECME EDTA EIA /e FAD FET FIA G GOD G6P-DH HBg HCG adenosine diphosphate a-fetoprotein antibody antigen alanine aminotranferase alkaline phosphatase aspartate aminotransferase adenosine triphosphate benzoquinone bovine serum albumin cholesterol ester hydrolase creatine kinase chemically modified electrode cholesterol oxidase concanavalin A coefficient of variation (relative standard deviation) layer thickness diffusion coefficient enzyme potential Enzyme Classification enzyme-chemically modified electrode ethylene diamine tetraacetic acid enzyme immunoassay enzyme loading factor flavin adenine dinucleotide field effect transistor flow injection analysis amplification factor glucose oxidase glucose-6-phosphate dehydrogenase hepatitis B surface antigen human chorionic gonadotropin... 

Cholesterol ester hydrolase Concanavalin A ConA-Sepharose 155... 

This enzyme (triacylglycerol acyl-hydrolase) has a molecular mass of approximately 42 kDa (Hide, Chan, and Li 1992) and a short half-life of about 1-3 h in dogs. Pancreatic lipase is secreted in its active form, and this activity is enhanced by colipase and bile salts the enzyme hydrolyzes triglycerides to monoglycerides. Other lipases— phospholipase a, phospholipase b, and cholesterol ester hydrolase—are also secreted by the pancreas. 

It appears there are two main reasons for the accumulation of cholesterol esters in rats that are fed HEAR oil or erucic acid containing diets. First, the cholesterol ester hydrolase fails to increase in activity when these rats are stressed, while in control rats, when stressed, the enzyme doubles its activity (Beckett and Boyd, 1975). Second, cholesteryl erucate, which accumulates in the adrenals of rats fed HEAR oil, is only slowly hydrolyzed by the enzyme, i.e., at 25-30% of the rate of cholesteryl oleate. This may be very significant, since there is considerable cholesteryl erucate accumulation in the adrenal glands of rats fed diets high in erucic acid, i.e., this ester may constitute 29-35% of the total (Carroll, 1962 Walker and Carney, 1971). In addition, in these rats there was an accumulation of 8% cholesteryl eicose-noate. In agreement with this evidence of impaired adrenal function, the results indicate that plasma levels of one of the adrenal hormones, corticosterone, are lower in these rats than in control rats when exposed to an environmental stress (Walker and Carney, 1971 Budzynska-Topolowska eta/., 1975). 

Phospholipids are hydrolysed by pancreatic phospholipase Aj (phosphatidylcholine 1-acylhydrolase) and phospholipase A2 (phosphatidylcholine 2-acylhydrolase) present as a zymogen that requires activation by trypsin. The products of 1,2-diacyl-s -glycero-3-phosphocholine breakdown are fatty acids and lysophospholipids, that is, 2-acyl-s -glycero-3-phosphocholine and l-acyl-s -glycero-3-phosphocholine, respectively. Cholesterol esters are hydrolysed by pancreatic steryl ester acylhydrolase (cholesterol ester hydrolase) to give cholesterol and fatty acids. 

The cholesterol esters present in the intestinal lumen during digestion are rapidly hydrolyzed to the free alcohol and fatty acids[5]. Vahouny et al. showed that a pancreatic enzyme - cholesterol esterase or cholesterol esters hydrolase - is responsible for both the hydrolysis of cholesterol esters in the intestinal lumen and the esterification of the absorbed cholesterol in the intestinal mucosa[6,26] Because of the pH, the nature of the substrate and other undefined factors the reaction is directed towards hydrolysis in the lumen and towards esterification in the mucosa[5]. Although the ideal substrate for hydrolysis seems to be micellar cholesterol [27], an action of the enzyme at the oil-water interface of the lipid droplets cannot be excluded. The pancreatic origin of the rat cholesterol esterase has been repeatedly suggested, since in absence of pancreatic juice both hydrolysis of cholesterol esters and cholesterol absorption are significantly lower[28]. 

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