Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sterol O-Acyltransferase 2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1979

Serum and liver lipid composition and lecithin: cholesterol acyltransferase in horses, Equus caballus.

1. The lipid composition of serum and liver and some properties of serum lecithin: cholesterol acyltransferase of the horse were investigated. 2. Phospholipids and cholesterol were the major components of serum lipids and the concentration of triglyceride was considerably low. The concentration of liver lipids was comparable with that of other mammals. 3. Fatty acid composition of serum cholesterol ester resembled that of the 2-position of lecithin, except palmitic acid. 4. The activity of serum cholesterol esterifying enzyme was found to be 0.03-0.09 mumol/hr per ml. There was an equimolar decrease in free cholesterol and lecithin during incubation, and changes in unsaturated fatty acids in these two components were in good agreement. 5. Cholesterol esterification was reversibly inhibited by 5,5'-dithiobis-(2-nitrobenzoic acid). The acyl-transferase had a specificity for linoleic acid.

Animals↗
PubMed1979

Interactions of a photosensitive analog of cholesterol with hydroxymethyglutaryl-CoA reductase (NADPH) and acyl-CoA:cholesterol acyltransferase.

25-Azido[25-(3)H]norcholesten-3beta-ol, a radioactive photosensitive analog of cholesterol, was synthesized as a probe to study lipid-protein interactions [Stoffel, W. & Klotzbücher, R. (1978) Hoppe-Seyler's Z. Physiol Chem. 359, 199-209]. Upon UV irradiation a reactive nitrene is generated which can insert into carbon-hydrogen bonds of proteins to form covalent linkages. The compound has properties similar to those of cholesterol. When administered intravenously to rats it was transported to the liver, and within 4 hr it was found in all of the subcellular fractions, accounting for 8% of the microsomal sterol content. Concomitantly, it altered the activities of two membrane-bound enzymes. 3-Hydroxy-3-methylglutaryl (HMG)-CoA (NADPH) reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34] activity was reduced to 20% of control values, and acyl-CoA:cholesterol acyltransferase (ACAT; acyl-CoA:cholesterol O-acyltransferase, EC 2.3.1.26) was stimulated at least 2-fold. Esterified products of the analog were found in both blood and liver, and no evidence was obtained for production of any hydroxylated or polar derivatives. UV irradiation of microsomes increased the radioactivity bound to the protein fraction and decreased it in the total lipid extract; in parallel a sharp decline in ACAT activity but unaltered HMG-CoA reductase activity was observed. These results are interpreted as a possible consequence of crosslinking of the sterol to the enzyme proteins and discussed in view of the evidence that HMG-CoA reductase is an extrinsic and ACAT an intrinsic membrane protein.

Acyltransferases↗
PubMed1979

Esterification of cholesterol in fish plasma: studies on the cholesterol esterifying enzyme in plasma of char (Salmo alpinus L.).

1. Plasma of sea char (Salmo alpinus L.) has the ability to esterify cholesterol in vitro. Heat inactivation of the plasma totally inhibited the esterification. 2. Arrhenius plot of the esterification of [3H]cholesterol was linear in the temperature range 5-35 degrees C. 3. Cholesterol esterification in sea char plasma could not be reversibly inhibited by sulphydryl-blocking agents. Total equilibration of the added [3H]cholesterol and the endogenous cholesterol could therefore not be obtained. 4. Comparison of esterification of endogenous and labelled cholesterol revealed that the isotopic method was valid only in qualitative measurements.

Animals↗
PubMed1978

Lecithin:cholesterol acyltransferase in partial ileal bypass rats.

In cholesterol-fed rats 6 weeks after partial ileal bypass, there was a significant (56%) decrease in serum cholesterol. Also, the concentration of very low density lipoprotein (VLDL) cholesterol was dramatically reduced after operation. However, after the operation, the percentage of high density lipoprotein (HDL) cholesterol was very high, i.e., 45% of the total lipoprotein cholesterol, whereas it was only 25% before operation. The initial rate of lecithin:cholesterol acyltransferase (LCAT), when assayed according to Stokke & Norum, showed an increase from 29 +/- 2 mumole/ml/h for non-operated cholesterol-fed controls to 121 +/- 7 mumole/ml/h after operation (p less than 0.01). After intestinal bypass the extrahepatic triglyceride lipase activity in serum was reduced by 60%, and there was no significant difference in hepatic triglyceride lipase. These observations indicate that in partial ileal bypass, the low serum cholesterol is due to the high HDL cholesterol and the high LCAT activity.

Animals↗
PubMed1979

Determination of lecithin:cholesterol acyltransfer in mouse plasma and the influence of mercaptoethanol and sulphydryl blocking agents on its activity.

1. The cholesterol esterifying activity in mouse plasma has been identified as lecithin:cholesterol acyltransferase (LCAT) on the basis of stoichiometric data, predominant transfer of polyunsaturated fatty acids, wide pH optimum and inhibition of esterification by phospholipase A2 and sulphydryl blocking agents. The esterifying activity differed from that present in plasma of man, rat and other species since it was partially inhibited by mercaptoethanol and other thiols. 2. Stoichiometric correlations between unesterified cholesterol, lecithin and lysolecithin were not exact, suggesting possible involvement of other enzymes in the overall esterification process during in vitro incubation of mouse plasma. 3. The initial rate of cholesterol esterification was determined by in vitro incubation of mouse plasma, whose cholesterol had been labelled by prior in vivo injection of 3H-mevalonic acid. The mean rate was 281 +/- 74 nmol/ml/hr (mean +/- S.D., n = 12) and correlated with unesterified cholesterol concentration (r = 0.73, P less than 0.01).

Animals↗
PubMed1978

Plasma cholesterol esterification and plasma lipoproteins in bile-duct-ligated dogs.

To study the lipoprotein changes in cholestasis while the capacity for plasma cholesterol esterification was normal, the common bile duct was ligated in dogs and plasma investigated 8 h and 48 h later. The plasma concentration of cholesteryl esters was slightly increased, concomitant with a tendency toward an increase in the activity of lecithin:cholesterol acyltransferase (LCAT). The content of cholesteryl esters in the main lipoprotein classes was normal. Marked alteration in the low density lipoproteins (LDL) and the high density lipoproteins (HDL) took place and were essentially similar 8 h and 48 h after bile duct ligation. In LDL, (density 1.006--1.019 g/ml) and LDL2 (density 1.019--1.063 g/ml) an increase in the content of polar lipids was observed, and in LDL2 heterogeneity in particle size was demonstrated by gelfiltration on 2% agarose and by electron microsopcy. Large myelin structures, flattened disc-shaped particles, and particles with the appearance of normal LDL2 were present. HDL isolated after operation was characterized by a decreased protein/lipid ratio and an increased content of phospholipids. By gelfiltration on Sephadex G-200 and by electron microscopy changes in particle size were observed, with the presence of disc-shaped particles with a tendency in form rouleaux. These results demonstrate that marked lipoprotein changes occur as early as 8 h after bile duct-ligation in dogs and indicate that a deficient LCAT mechanism is present in cholestasis even with normal or high plasma LCAT activity.

Animals↗
PubMed1979

Lecithin-cholesterol acyltransferase and the lipoprotein abnormalities of parenchymal liver disease.

1. Detailed studies have been made of the plasma lipoprotein abnormalities in parenchymal liver disease to test the hypothesis that the abnormalities would correlate with plasma lecithin-cholesterol acyltransferase (LCAT) activity. 2. When LCAT was high, very-low-density-lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility. When LCAT was low, VLDL concentrations were greatly reduced. 3. With high LCAT low-density lipoproteins (LDL) were normal. The LDL particles found with low LCAT activity were of normal size but of abnormal composition, being triglyceride rich and cholesteryl ester poor. Regardless of LCAT activity LDL were present in normal amounts. 4. High-density lipoproteins (HDL) were normal in composition and electron-microscopic appearance when LCAT activity was high. When LCAT activity was low HDL were abnormal in composition and 'stacked discs' were seen on electron microscopy. 5. These results suggest that low LCAT activity may be the cause of at least some of the lipoprotein changes of parenchymal liver disease.

Adult↗
PubMed1979

Physical exercise modifies the effect of high cholesterol-sucrose feeding in the rat.

1. Adult male rats were fed a basic chow (less than 0.01% cholesterol) and the same diet modified to contain 0.2% cholesterol and 20% sucrose. 2. Cholesterol-sucrose diet increased the erythrocyte cholesterol and the liver cholesterol. This diet decreased the epididymal fat weight and the biliary cholesterol and it improved the micellar solubility of cholesterol in the bile. 3. Swimming daily for 1 h for 94 days modified the effect of cholesterol-sucrose feeding: it induced plasma lecithin-cholesterol acyltransferase (LCAT), it decreased erythrocyte cholesterol, plasma total and unesterified cholesterol, and adipose tissue phospholipids to a level even beyond that of the animals on the basic chow. These changes in lipid levels induced by exercise suggest an important role of LCAT in cholesterol transport. 4. Exercise did not effect micellar solubility of cholesterol in the bile probably because cholesterol biosynthesis was already suppressed by dietary cholesterol. 5. Exercise promotes cholesterol esterification and transport from the peripheral tissues to the liver not only on a low cholesterol diet (our previous reports) but also when feeding a diet high in cholesterol and sucrose.

Animals↗
PubMed1975

Synthesis of cholesterol esters in the plasma and liver of sheep.

A study was made with sheep on the formation in vitro of long chain fatty acid esters of cholesterol by the lecithin-cholesterol-acyltransferase system present in the plasma and the acyl CoA-cholesterola cyltransferase system present in the liver. The rate of cholesterol esterification in the plasma was 0.024 mumoles/ml/hr. The relative pattern of fatty acids esterified during incubation of the plasma remained constant over the 8 hr period of incubation and was similar to the fatty acids in the plasma cholesteryl esters before incubation began and to the fatty acids in the 2-position of the plasma lecithin. The predominant cholesteryl esters synthesized contained monoenoic and dienoic fatty acids. Unlike the bovine, there was no apparent discrimination in favor of the 18:2 containing species of plasma lecithin as donors of fatty acids. This difference could be accounted for by the similarity in the 18:2 content of the phospholipids present in the high density (density greater than 1.062 and less than 1.21) and the low density (density greater than 1.006 and less than 1.063) lipoprotein fractions of the sheep plasma. The possibility of some discrimination against 20:4 during cholesterol ester synthesis in the plasma of the sheep cannot be excluded. In the liver, the predominant cholesteryl esters synthesized contained saturated and monoenoic fatty acids; cholesteryl linoleate was synthesized to a very much less extent. There was considerable similarity between the composition of the unesterified fatty acid fraction of the liver before incubation began and the fatty acid composition of the cholesteryl esters synthesized during incubation. Addition of sonicated suspensions of free fatty acidsaltered markedly the fatty acid pattern of the cholesteryl esters synthesized by the liver slices. From the evidence presented it is concluded that the cholesteryl esters in sheep plasma are syntheized mainly by the plasma lecithin-cholesterol-acyltransferase system. The results are discussed in relation to cholesterol esterification systems demonstrated in the plasma and liver of monogastric animals.

Animals↗
PubMed1976

The influence of LP-X and other lipoproteins associated with hepatic dysfunction on the activity of lecithin:cholesterol acyltransferase.

A study was made of the in vitro effects of the abnormal serum lipoproteins associated with liver disease on the activity of the enzyme lecithin:cholesterol acyltransferase. At lipoprotein concentrations equivalent to those found in hepatic disease sera, the results indicate that: (1) LP-X levels greater than 2.5 mg/ml produced total inhibition of enzyme activity. (2) LP-X levels remained constant even up to 36 h incubation, despite active cholesterol esterification in the presence of LP-X concentrations less than 2.5 mg/ml. In addition, the specific activity of radiolabelled LP-X, and its electrophoretic properties remained unchanged after incubation showing that the molecule remained intact. (3) Low density lipoproteins other than LP-X stimulated the enzymes activity, but this effect was overcome by LP-X. (4) Additional concentrations of high density lipoproteins also produced enhancement of enzyme activity, but at higher levels inhibition was seen. LP-X prevented the enhancement of lecithin:cholesterol acyltransferase activity. (5) Small samples of pure LP-X, obtained with the minimum of physical manipulation, showed a complete absence of cholesterol ester and triacylglycerol from the molecule. The implications of these results are discussed, particularly in relation to other reports which have presented evidence that LP-X is a substrate for lecithin:cholesterol acyltransferase.

Acyltransferases↗
PubMed1976

Secretion of lecithin: cholesterol acyltransferase from isolated rat hepatocytes.

1. Lecithin:cholesterol acyltransferase is secreted from isolated rat heptocytes. 2. The secretion is stimulated when serum is added to the incubation medium. 3. Optimal conditions for secretion are: 5-10(6) hepatocytes per ml, 5 h incubation, pH 7.3-7.4 and 25% serum in the incubation medium. 4. Concomitantly with the secretion of lecithin:cholesterol acyltransferase there is a secretion of unesterified cholesterol and triacylglycerol. 5. Colchicine or cycloheximide in the incubation medium inhibits secretion of lecithin:cholesterol acyltransferase.

Acyltransferases↗
PubMed1977

Uptake and degradation of cholesterol ester-labelled rat plasma lipoproteins in purified rat hepatocytes and nonparenchymal liver cells.

1. A new method for isolation and purification of rat liver hepatocytes and nonparenchymal cells by differential centrifugation is described. 2. Cholesterol ester-labelled lipoproteins (prepared by the action of lecithin: cholesterol acyltransferase) intravenously injected were taken up by hepatocytes and nonparenchymal cells. 3. Hepatocytes and nonparenchymal cells in suspension were able to take up and hydrolyse the cholesterol ester portion of lipoproteins. 4. Uptake of cholesterol ester labelled whole rat plasma and high density lipoproteins (HDL) increased with increasing concentrations until a distinct saturation level was reached in hepatocytes. In nonparenchymal cells there was no saturation of lipoprotein uptake. 5. Concanavalin A inhibited cholesterol ester-labelled lipoprotein uptake in hepatocytes, indicating that the uptake at least partially depends on carbohydrate sites on the cell surface. The uptake in nonparenchymal cells was unaffected of concanavalin A. 6. The specific activity of the acid cholesterol ester hydrolase was the same in homogenates from hepatocytes and nonparenchymal cells while acyl-CoA: cholesterol acyltransferase was found almost exclusively in hepatocytes.

Acid Phosphatase↗
PubMed1978

Lecithin--cholesterol acyltransferase and the lipoprotein abnormalities of obstructive jaundice.

1. We have studied the plasma lipoprotein abnormalities in obstructive jaundice to test the hypothesis that the abnormalities would correlate with plasma lecithin--cholesterol acyltransferase activity. 2. Very-low-density lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility when lecithin--cholesterol acyltransferase activity was high. When it was low VLDL had abnormal composition and ran in the beta position. 3. With high lecithin--cholesterol acyltransferase activity, low-density lipoprotein (LDL) was normal and cholestatic LDL (LP-X) was not found. With low lecithin--cholesterol acyltransferase activity up to three LDL fractions were found: (i) large triglyceride-rich particles, (ii) LP-X and (iii) a triglyceride-rich cholesteryl ester-poor particle of normal dimensions. 4. High-density lipoprotein (HDL) concentrations correlated with lecithin--cholesterol acyltransferase activity and HDL were normal in composition and electron-microscopic appearance when the activity was high. When lecithin--cholesterol acyltransferase activity was low HDL was abnormal in composition and 'stacked discs' were seen on electron microscopy as well as normal spherical particles. 5. These results suggest that low lecithin-cholesterol acyltransferase activity may cause at least some of the lipoprotein changes of obstructive jaundice.

Adult↗
PubMed1979

Acyl-coenzyme A--cholesterol acyltransferase activity in human liver.

1. In the presence of CoA and ATP, human liver microsomes catalyse the incorporation of [14C]oleate or [14C]cholesterol into cholesteryl oleate, thus demonstrating the presence of acyl-coenzyme A-cholesterol acyltransferase (cholesterol acyltransferase) in human liver. 2. The enzyme has properties similar to those of rat liver enzyme and with both the concentration of endogenous cholesterol in the microsomal fraction is adequate to support a constant initial rate of esterification. However, unlike the rat liver enzyme, the human cholesterol acyltransferase does not efficiently utilize added cholesterol as substrate. 3. The activity of cholesterol acyltransferase in human liver was 25% of that measured in rat liver under similar conditions of assay.

Acyltransferases↗
PubMed1975

Plasma lipoprotein abnormalities in a case of primary high-density lipoprotein (HDL) deficiency.

A 53-year-old patient with primary HDL-deficiency is reported. About 2% of the normal concentration of alpha1 HDL was present in his plasma. The alpha1-high-density-lipoproteins separated into two fast-moving components in polyacrylamide gel electrophoresis. The Apo HDL contained both the main apolipoproteins, Apo A-I and Apo A-II, but in disproportionally reduced amounts, the concentration of Apo A-I being reduced about 360-fold, and that of Apo A-II about 14-fold. Concomitantly, the amount of the Apo C polypeptides in the HDL-fractions was decreased to about 5.5% and the activity of the enzyme lecithin cholesterol acyltransferase (EC 2.3.1.4.3) in plasma was found to be only 40% of normal. Apoprotein D was present in the LDL in association with Apo B, forming an abnormal, fast-moving LDL-complex. Apo A-I and Apo A-II were both of normal size as determined by SDS-PAGE, and reduction with thiols resulted in the shift of the M.W. of Apo A-II from 17,000 daltons to about 8,500 daltons. Both proteins were found in the same position as their normal counterparts in analytical isoelectric focusing. The most likely explanation for the multiple lipoprotein abnormalities seems to be that a defect in the regulation or structure of Apo A-I is the basis of the HDL-deficeincy.

Blood Protein Electrophoresis↗
PubMed1979

The hepatic secretion of lecithin: cholesterol acyltransferase in rats with increased secretion of triglycerides due to ventromedial hypothalamic lesions.

Lecithin:cholesterol acyltransferase (LCAT) is postulated to take care of excess cholesterol formed during metabolism of triglyceride (TG)-rich lipoproteins. To test this hypothesis the relationship between secretion of LCAT and TG have been investigated in rats with ventromedial hypothalamic lesions which lead to increased hepatic secretion of TG. 1. The increased plasma concentration of TG in rats with ventromedial hypothalamic lesions was positively correlated to the activity of LCAT in plasma. 2. Incubation of hepatocytes isolated from such rats revealed a positive linear correlation between secretion of TG and of LCAT. 3. The secretion of unesterified cholesterol was neither correlated to the secretion of the acyltransferase nor to the TG.

Animals↗
PubMed1975

Lecithin:cholesterol acyl transfer in plasma of normal persons in relation to lipid and lipoprotein concentration.

Information concerning variation in the lecithin:cholesterol acyl transfer (LCAT) rate in normal persons is scanty. We have therefore analyzed the LCAT rate and the lipid and lipoprotein concentrations in the plasma of healthy normolipidemic persons 20-60 years of age, 40 men and 40 women. 10 per decade and sex. Interindividual variation in molar LCAT rate was 57-130 mumol-u(-1)-h-1 (mean +/- 2 S.D.) with no sex difference. Intraindividual variation of molar LCAT rate studied in 8 women and 9 men was shown to be greater than expected from methodological error and was not explainable by the small changes in plasma lipid concentration during the observation period. In the women the molar LCAT rat was lower during the preovulatory phase of the menstrual cycle than during the postovulatory phase. There was positive correlations between the molar LCAT rate and most of the lipid parameters in plasma. By partial correlation analysis a positive correlation was shown between LCAT rate and triglyceride concentration irrespective of other lipid parameters. Keeping triglyceride concentration constant, there was a positive correlation between molar LCAT rate and total phospholipid, unesterified cholesterol, esterified cholesterol, or low-density lipoprotein (LDL) cholesterol concentration. No correlation was found between high-density lipoprotein (HDL) lipid concentration and LCAT rate. Thus in normal subjects there seems to be a direct relation between very low density lipoprotein and LDL lipid concentration and molar LCAT rate but no relation between HDL lipid concentration and LCAT rate.

Acyltransferases↗
PubMed1976

Regulation of plasma lecithin:cholesterol acyltransferase in man. I. Increased activity in primary hypertriglyceridemia.

Patients with primary hypertriglyceridemia have been reported to manifest increased in vivo turnover of plasma cholesteryl esters. To ascertain if this is due to plasma lecithin:cholesterol acyltransferase (LCAT) and to explore a possible link between triglyceride and cholesteryl ester turnover, we have measured LCAT in 15 patients with Type IV, 2 with Type V, 1 with Type III, and 9 with Type II B hyperlipoproteinemia. LCAT was significantly elevated (p less than 0.001) in hypertriglyceridemic subjects, regardless of lipoprotein pattern. In the Type IV group, but not in normal subjects, LCAT correlated significantly with measures of very low-density lipoprotein (VLDL) elevation, including plasma triglycerides and particularly VLDL-unesterified cholesterol, but not with body weight or substrate high-density lipoprotein (HDL) lipid levels. On repeated determinations in individual subjects, a relationship between triglyceride fluctuations and LCAT could be demonstrated in only one subject over an extreme range of triglyceride levels. Analysis of lipoprotein lipids revealed that the ester:free cholesterol ratio in VLDL was increased in hypertriglyceridemia, but was not correlated with enzyme level. In vitro removal of endogenous VLDL or addition of VLDL from lipemic plasmas to normal plasmas was without effect on enzyme activity. Regulation of enzyme activity does not appear to be a direct function of VLDL level.

Acyltransferases↗