Lecithin:cholesterol Acyl Transfer Research Articles

Plasma cholesterol esterification rate in hyperlipoproteinaemia: relation to cholesterol elimination.

The present study was undertaken to determine the relationship between plasma lecithin: cholesterol acyl transfer (LCAT) rate and cholesterol and bile acid turnover in hyperlipidaemia. Nineteen healthy controls, 19 patients with hyperlipoproteinaemia (HLP) type IIa and 12 patients with HLP type IV were studied under standardized dietary conditions. Bile acid kinetics was determined with the aid of [14C]labelled cholic acid and chenodeoxycholic acid. In the hyperlipidaemic patients, cholesterol balance was calculated as the sum of bile acid synthesis plus daily faecal excretion of neutral C27 steroids minus dietary intake of cholesterol. The plasma LCAT rate was determined simultaneously. The mean values of bile acid formation, cholesterol balance, and LCAT rate in HLP type IV patients exceeded those in HLP type IIa patients or in the controls. An increased plasma LCAT rate was found among HLP type IV patients with and without evidence of cardiovascular disease. Plasma LCAT rate correlated positively with bile acid formation (Rs = +0.78, p less than 0.01) and cholesterol balance (Rs = +0.88, p less than 0.002) in HLP type IV. No such relationships were obtained in the controls or in HLP type IIa. It is suggested that an increased production and/or flux of VLDL in HLP type IV is linked to an enhanced plasma LCAT rate and to an increased formation and metabolism of cholesterol in the liver.

Plasma cholesterol esterification rate in hyperlipoproteinaemia: Relation to cholesterol elimination

The present study was undertaken to determine the relationship between plasma lecithin: cholesterol acyl transfer (LCAT) rate and cholesterol and bile acid turnover in hyperlipidaemia. Nineteen healthy controls, 19 patients with hyperlipoproteinaemia (HLP) type IIa and 12 patients with HLP type IV were studied under standardized dietary conditions. Bile acid kinetics was determined with the aid of [14C]labelled cholic acid and chenodeoxycholic acid. In the hyperlipidaemic patients, cholesterol balance was calculated as the sum of bile acid synthesis plus daily faecal excretion of neutral C27 steroids minus dietary intake of cholesterol. The plasma LCAT rate was determined simultaneously. The mean values of bile acid formation, cholesterol balance, and LCAT rate in HLP type IV patients exceeded those in HLP type IIa patients or in the controls. An increased plasma LCAT rate was found among HLP type IV patients with and without evidence of cardiovascular disease. Plasma LCAT rate correlated positively with bile acid formation (Rs = +0.78, p<0.01) and cholesterol balance (Rs = +0.88, p<0.002) in HLP type IV. No such relationships were obtained in the controls or in HLP type IIa. It is suggested that an increased production and/or flux of VLDL in HLP type IV is linked to an enhanced plasma LCAT rate and to an increased formation and metabolism of cholesterol in the liver.

Profound alterations of the lipoprotein metabolism during danazol treatment in premenopausal women

Twelve women with pelvic endometriosis were treated with 600 mg of danazol daily for 24 weeks. The molar and fractional lecithin:cholesterol acyl transfer (LCAT) rates and the concentrations of cholesterol, phospholipids, and triglycerides were determined in plasma and in the very low-density lipoprotein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and HDL2 and HDL3 fractions before, during, and after the medication. After 2 weeks the HDL, HDL2, and HDL3 cholesterol concentrations were reduced by 49%, 73%, and 29%, respectively, while the LDL level was increased by 14%. The molar and fractional LCAT rates decreased during treatment, and these reduced LCAT rates are consistent with a reduced fractional LDL removal. Within 8 weeks after cessation of medication, all parameters had returned to the pretreatment levels.

Lecithin: Cholesterol acyl transfer rate and high density lipoprotein level in coronary artery disease

The lecithin:cholesterol acyl transfer (LCAT) reaction occurs in connection with the high density lipoproteins (HDL) and might have importance for the development of atheromatosis. The LCAT rate and the lipoprotein concentrations in plasma were therefore determined in 82 patients, 40–60 years old, with incapacitating angina pectoris and significant lesions at coronary angiography. Thirty-eight cases were normolipidemic and 22 had type IV hyperlipidemia while the others had different types of hypercholesterolemia (n = 7) or were pharmacologically treated for previously diagnosed hyperlipidemia (n = 11) or diabetes mellitus. The normolipidemic group and the type IV group with coronary artery disease were separately compared to one normolipidemic (n = 44) and one type IV hyperlipidemic (n = 29) control group of healthy subjects of about the same age. The fractional LCAT rate (% · h −1) was lower in patients compared to controls both regarding the normolipidemic and type IV subjects. The molar LCAT rate (μmol · 1 −1 · h −1) did not differ between normolipidemic cases and controls while it was lower in type IV patients with coronary artery disease than in the type IV controls. The HDL total cholesterol (TC) concentration and the HDL-TC/TC ratio were lower in normolipidemic cases than in normolipidemic controls while both cases and controls with type IV hyperlipidemia showed equally low levels of these parameters. In conclusion, both a reduced fractional LCAT rate and a decreased HDL-TC/TC ratio might be indicators of disturbances of the cholesterol ester metabolism and might contribute to the development of coronary atheromatosis.

A comparative study of lecithin:cholesterol acyltransfer in plasma of five species of amphibians from Northeast Brazil

1. 1. Lecithin:cholesterol acyltransfer (LCAT) was studied radiochemically in plasma from five species of Salienta, Bufo paracnemis, B. granulosus, Rana palmipes, Hyla raniceps and Leptodactylus ocellatus. 2. 2. Large inter- and intra-species variations in plasma LCAT activity were observed but activity correlated significantly with plasma triglyceride concentrations. 3. 3. The effects of pH and inhibitors on LCAT activity in amphibian plasma were similar to those described for mammalian plasma. 4. 4. Storage at −15°C for several weeks reduced LCAT activity in amphibian plasma but not in human plasma. 5. 5. Cholesteryl esters synthesised by LCAT were predominantly monoenoic in plasma of Bufo species and polyenoic in plasma of other species.

Lecithin : cholesterol acyl transfer (LACT) and fatty acid composition of lecithin and cholesterol esters in young male myocardial infarction survivors

Lecithin : cholesterol acyl transfer (LCAT) and relative fatty acid composition of serum lecithin and cholesterol esters were studied in 20 young male survivors of myocardial infarction (MI). Comparisons were made with controls matched for serum cholesterol. There was no difference in LCAT rate between MI patients and controls. The relative content of arachidonic acid in cholesterol esters was higher in MI patients. The fatty acid composition of lecithin and cholesterol esters suggests an equal transfer of linoleic and oleic acids from lecithin to cholesterol. Furthermore negative correlations were found between LCAT and linoleic acid content of lecithin ( r = −0.43, P < 0.01) and cholesterol esters ( r = −0.45, P < 0.01). This inverse relationship does not seem to be linked to substrate specificity, but rather to be mediated by influences in common on serum lipid content and turnover.

Lecithin: Cholesterol acyl transfer rate and high density lipoproteins in plasma during dietary and clofibrate treatment of hypertriglyceridemic subjects

Effects of lipid-lowering treatment on the lecithin: cholesterol acyl transfer (LCAT) rate and the concentrations of lipids and high density lipoproteins (HDL) lipids in plasma were determined in hypertriglyceridemic subjects. Thirty-nine subjects were studied before and after two months on a weight reducing diet. Twenty subjects were studied also one month after the addition of clofibrate to the dietary regimen. After two months on the diet the mean body weight had decreased by 4.5%. There were reductions in the mean plasma concentrations of triglycerides (TG) by 18% and in total cholesterol (TC), unesterified cholesterol (UC) and phospholipids (PL) by 12%. The mean HDL-TC concentrations increased by 10%, while the mean HDL-PL concentration was unchanged. During two months of diet the mean molar LCAT rate decreased by 17% and the mean fractional LCAT rate was reduced by 6%. One month after the addition of clofibrate there were reductions in the mean plasma concentrations of TG by 43% and of TC, UC and PL by 15%. The mean HDL-TC concentration increased by 22%, while the mean HDL-PL concentration was enhanced by 9%. The mean molar LCAT rate decreased by 10%, based on reductions in the type IV subjects with high molar LCAT rates before the clofibrate treatment. The mean fractional LCAT rate was not changed in the type IV subjects but increased in the type IIb and type III subjects during clofibrate therapy. The changes in the molar LCAT rate correlated positively with the changes in the body mass after two months on the diet and with the changes in the concentrations of TG, UC and PL in plasma obtained with both kinds of treatment. The changes in the fractional LCAT rate were negatively correlated with the changes of low density lipoprotein-TC concentrations during both kinds of treatment.

Lecithin: Cholesterol Acyl Transfer Rate in Plasma and its Relations to Lipoprotein Concentrations and to Kinetics of Bile Acids and Triglycerides in Hyperlipoproteinemic Subjects

The lecithin:cholesterol acyl transfer (LCAT) rate and the concentrations of lipids and lipoproteins in plasma were determined in 85 normolipidemic reference subjects and in 89 subjects with different types of hyperlipoproteinemia (38 type 11a, 9 type lib. 2 type III. 38 type IV and 2 type V). The mean molar LCAT rate was lower in the reference group than in all types of hyperlipoproteinemia. The type IV and type V subjects had the highest molar LCAT rates. The mean fractional LCAT rate was reduced in type Ha and elevated in type IV compared to the reference group. In the hyperlipoproteinemic subjects the molar LCAT rate correlated positively with the triglyceride (TG)or the very low density lipoprotein (VLDL) concentration in plasma and with the body weight. The fractional LC AT rate correlated negatively with the LDL-total cholesterol (TC) concentration in plasma. After two months on a weight-reducing diet the mean molar and fractional LCAT rates were reduced by 17% and 6% respectively in 39 hypertriglyceridemic subjects. The changes of the molar LCAT rate correlated positively with the changes of the TG. unesterified cholesterol, and phospholipid concentrations in plasma and with the changes of the body weight. The changes of the fractional LCAT rate correlated negatively with the changes of the LDL-TC concentration in plasma. The production rate of bile acids and the turnover of endogenous TG, which were determined in 7 type IV subjects, correlated positively with the molar LCAT rate. There was no correlation between the bile acid production and the molar LCAT rate in 12 type Ila subjects. The results indicate that there are close relations between the production rate of cholesteryl esters (CE)in plasma and the production rate of VLDL and bile acids in type IV subjects. It is suggested that the molar LCAT rate determined in vitro might reflect the turnover of CE in plasma in vivo.

Lecithin: Cholesterol acyl transfer rate in plasma and its relation to lipid and lipoprotein concentrations in primary hyperlipidemia

Plasma lecithin: cholesterol acyl transfer (LCAT) rate and concentrations of lipids in plasma and lipoproteins were studied in 107 hyperlipidemic subjects. In all types of hyperlipoproteinemia LCAT rates were higher than in a normolipidemic reference group. LCAT rates were highest in type IV and V. There was a considerable overlap of LCAT rates between type IIa, IIb and reference subjects. The LCAT rate correlated positively with very low density lipoprotein concentration, body mass and excess body mass. Low density lipoprotein concentration correlated positively with the LCAT rate only in the reference group. The high density lipoprotein concentration correlated negatively with the LCAT rate. It was suggested that the LCAT rate in vitro reflects the in vivo turnover of cholesterol esters as a part of the turnover of apoprotein-B containing lipoprotein complexes in plasma. The results might then indicate an inflow rate of lipoproteins in plasma that is increased in most type IV cases but normal or only moderately increased in type Ha and IIb subjects. Analysing the relations between the LCAT rate and the concentrations of lipids in plasma by multiple regression indicated hypothetically deficiencies of lipoprotein removal from plasma in half of type Ha and one third of type IIb subjects.

Studies on plasma lipid and phospholipid composition in pernicious anemia before and after specific treatment.

Patients with pernicious anemia (PA) have been compared with a reference group concerning the concentration of lipids in plasma before (34 cases) and after (15 cases) treatment with vitamin B12. The lipid parameters in plasma and in postheparin plasma have been measured before and after 6 hours' incubation at 37degree C before and after specific treatment. In a limited number of cases the lecithin: cholesterol acyl transfer (LCAT) rate has been determined. In relapse, the PA cases showed increased free fatty acid (FFA) and triglyceride (TG) concentrations but decreased concentrations of total cholesterol (TC), unesterified cholesterol (UC) and all examined phospholipid fractions. After treatment, FFA remained unchanged and TG decreased, while TC and possibly also UC and the phospholipid frations were in line with reference levels. After incubations, UC and phosphatidylcholine (PC) decreased and lysolecithin (LL) increased. FFA increased and TG decreased. Incubation of postheparin plasma resulted in an augmented decrease in TG and PC and increase in FFA and LL, In relapse, the changes on incubation were less pronounced than after treatment. The LCAT was low but within the normal range before treatment in the six cases examined. After treatment, LCAT rates increased but were still normal in relation to the plasma lipid concentrations. The study showed a decreased net esterification of cholesterol and LL formation on incubation of plasma in PA cases in relapse. This finding might be explained by the low concentration of plasma substrates for the LCAT reaction and phospholipases. After treatment the concentration of lipid substrates was restored to normal, with subsequent normal LL formation and cholesterol esterification. The observations could also explain the frequent lack of stabilization of erythrocytes suspended in plasma of PA after incubation, resulting in virtually the same ESR after as before this procedure. Due to low LL formation following the insufficient substrate availability for LCAT and phospholipase, the previously reported critical level of the LL concentration is not reached and cannot achieve its normal reduction of the ESR.

Influence of Fat Ingestion on Lecithin:Cholesterol Acyl Transfer Rate in Plasma of Normal Persons

Lecithin:cholesterol acyl transfer (LCAT) rate in plasma and lipid concentrations in total plasma and high density lipoproteins (HDL) were determined before and after oral fat loads in healthy human subjects. The changes of LCAT rate after fat loading were compared to the effect of chylomicrons or lipid emulsions added in vitro to fasting plasma. After the fat loads there was an increase of mean molar LCAT rate simultaneous with an increase of mean phospholipid (PL) and HDL-PL concentration but not simultaneous with the increase of mean triglyceride (TG) concentration. Individual changes of molar LCAT rate correlated positively with changes of PL, HDL-PL, and unesterified cholesterol (UC) concentration but not with changes of TG concentration in the separate plasma samples after the fat loads. If only the maximal changes in each subject in any sample at any time after the loads were taken into account, the maximal increase of molar LCAT rate correlated positively with the maximal increase of TG concentration. Molar LCAT rate was not influenced by addition of chylomicrons in vitro but increased after addition of a PL emulsion. It is suggested that LCAT rate is stimulated by an excess of PL in plasma and substrate lipoproteins. This excess of PL may be created in vivo temporarily during chylomicron catabolism. The stimulation of LCAT rate by fat ingestion emphasizes the importance of LCAT as a connecting link between triglyceride and cholesterol metabolism.

Studies on Human Serum High-Density Lipoproteins: VI. Studies on a Cholesterol Ester-Releasing Reaction in Vitro

High-density lipoproteins (HDL) turn turbid during in vitro incubation, concomitant with the formation of a cholesterol ester-rich lipoprotein, designated HDL-sup. The increase in turbidity (A) formed in relation to incubation time (t) is an asymptotic function: A=Uo(1 - e-k1t), where Uo is the amount of HDL with the property of releasing HDL-sup and k1 the velocity constant of the reaction. The increase in turbidity and formation of HDL-sup was not related to cholesterol ester content of the incubated fraction nor to exogenous factors like bacterial growth. The in vitro incubation was accompanied by a cholesterol esterification with a mean production of 8 nmol cholesterol ester/mg HDL protein, but also by a more pronounced degradation of phosphatidyl choline, 148 nmol/mg HDL protein. These data indicate that the lipid changes are induced by a two-step lecithin:cholesterol acyltransfer (LCAT) reaction. This reaction caused in HDL lipids a consumption of surface material and an increase in 'lipid core', presumably leading to a weakening and disruption of the lipoprotein surface with a recombination of 'lipid core' material in the form of HDL-sup.

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.

Evaluation of an in Vitro Assay of Lecithin:Cholesterol Acyl Transfer Rate in Plasma

Crucial and previously criticized points in a slightly modified version of the Stokke-Norum assay of fractional lecithin:cholesterol acyl transfer (LACT) rate in plasma were studied. LCAT activity in the albumin added to the assay medium and negative influence of remaining organic solvent were important sources of error that it was necessary to eliminate. The assumption of equilibration of labeled cholesterol among lipoproteins in vitro was supported experimentally. Addition of isolated chylomicrons had no influence on initial LACT rate. Incubation time was decreased to 20 minutes to obtain a better estimate of initial LCAT rate in normals. Using gas-liquid chromatography to determine unesterified cholesterol concentration, the precision of measurement of molar LCAT rate was 5.2 per cent (coefficient of variation). Molar LCAT rate in healthy males 20-60 years of age was 56-130 mumol-1(-1)-h-1 (mean +/- 2 S.D.) and compared well with reports from other laboratories and in vivo measurements. At present this methodology is considered to be suitable for studies of LCAT and cholesterol turnover in different metabolic situations and clinical materials.

Cholesterol esterification and lipids in plasma and liver from newborn and young guinea pigs raised on milk and non-milk diet.

Plasma lecithin:cholesterol acyltransfer (LCAT), liver acyl-CoA:cholesterol acyltransfer (ACAT) and plasma and liver lipids were examined in newborn and young guinea pigs fed ordinary or a non-milk diet. LCAT in newborns was about 70% of the adult value, increased the first 3 days to values about three times the adult value, and decreased during the next 3 weeks to about adult value. Plasma lipids varied in a similar way. Liver ACAT in newborns was considerably higher than in adults. In young animals on non-milk diet the LCAT and ACAT were lower than in normally fed animals. LCAT was positively correlated to free cholesterol in plasma.

Studies on Human Serum High-Density Lipoproteins II. Isolation of Subfractions in the Cold

The lecithin cholesterol acyltransfer (LCAT) reaction appears to be responsible for the degradation of high-density lipoproteins (HDL). In an earlier study substrate HDL subfractions were isolated and purified in the presence of an SH-blocking agent, DTNB. Difficulties in removing all enzyme inhibition for the subsequent HDL degradation studies argued for the importance of finding an alternate ‘inhibited’ isolation procedure of HDL. HDL with a density of 1.067–1.20 g/ml was isolated and purified in the cold (0 to +4 °C) by repeated preparative ultracentrifugations and by gel chromatography. Five subfractions were obtained in the cold by the stepwise elution on hydroxyl-apatite column chromatography, using phosphate buffers of increasing molarity. Of the five subfractions, three, subfractions Ia (0.001–0.01 mol/1 phosphate buffer), II (0.05 mol/1 phosphate buffer), and III (0.15 mol/l phosphate buffer), appeared to be reproducible from one preparation to the other as judged from polypeptide and relative li...