Lecithin: cholesterol acyltransferase in liver disease

Lecithin: cholesterol acyltransferase (LCAT) activity in patients with liver disease has been found to be either normal or lower than normal, but no information on LCAT mass in these patients is available. In this study, LCAT mass concentration together with LCAT activity and cholesterol esterification rate were measured in the plasma of 19 patients with cholestatic liver disease and 21 patients with non-cholestatic liver disease. The LCAT mass in plasma correlated positively with serum albumin (r = 0.69, p less than 0.001) and pre-albumin (r = 0.77, p less than 0.001) and negatively with serum bilirubin (r = -0.42, p less than 0.01) and bile salts (r = -0.43, p less than 0.01), thus reflecting the severity of liver disease and liver protein synthesizing capacity. In plasma, LCAT mass concentration also correlated well with LCAT activity (r = 0.88, p less than 0.001) and cholesterol esterification rate (r = 0.73, p less than 0.001), thereby indicating that the decrease of LCAT activity and cholesterol esterification rate in liver disease is primarily a function of decreased LCAT mass.     

Lecithin: cholesterol acyltransferase in Down's syndrome

Based on earlier reports indicating that Down's syndrome may represent an atheroma-free human model, two groups of institutionalized subjects were compared with respect to various parameters of their plasma lipid transport system. One group of subjects was comprised of Down's syndrome subjects and the second, a group of mentally retarded individuals. Parameters measured included plasma cholesterol, triglyceride, HDL-cholesterol, apolipoprotein levels (A-I, B, C-III, and E), lecithin:cholesterol acyltransferase (LCAT) activity, body mass and blood pressure. Statistical analyses indicated no significant differences between the two groups except for the lower fractional rate of cholesterol esterification (% cholesterol esterified per hour, p = 0.0049) in the Down's syndrome subjects. Adjustment for the effects of body mass and age revealed no other significant differences between the two groups except for a lower molar rate of esterification (nmol cholesterol esterified X h-1 X ml-1, p less than 0.0063) in the Down's syndrome subjects. Additional differences between the two groups were revealed by partial correlational analyses of LCAT activity with the measured parameters or ratios of these parameters which suggests that the composition and/or metabolism of lipoproteins may differ between these two groups. Whether the lower LCAT activity and the other differences reflected by the correlational analyses contribute to the decreased incidence of atherosclerotic lesions in Down's syndrome remains to be elucidated.     

Lecithin: Cholesterol acyltransferase in liver disease

Lecithin: cholesterol acyltransferase (LCAT) activity in patients with liver disease has been found to be either normal or lower than normal, but no information on LCAT mass in these patients is available. In this study, LCAT mass concentration together with LCAT activity and cholesterol esterification rate were measured in the plasma of 19 patients with cholestatic liver disease and 21 patients with non-cholestatic liver disease. The LCAT mass in plasma correlated positively with serum albumin (r=0.69, p<0.001) and pre-albumin (r=0.77, p<0.001) and negatively with serum bilirubin (r=-0.42, p<0.01) and bile salts (r=-0.43, p<0.01), thus reflecting the severity of liver disease and liver protein synthesizing capacity. In plasma, LCAT mass concentration also correlated well with LCAT activity (r=0.88, p<0.001) and cholesterol esterification rate (r=0.73, p<0.001), thereby indicating that the decrease of LCAT activity and cholesterol esterification rate in liver disease is primarily a function of decreased LCAT mass.     

Lecithin: cholesterol acyltransferase activity and cholestyramine resin therapy in man.

The effect of the bile-acid-sequestering agent cholestyramine on esterification of plasma cholesterol has been studied in vitro. No change in the activity of plasma lecithin: cholesterol acyltransferase was found by either of the two assay methods employed. Similarly the resin did not produce any significant change in the ability of plasma to act as substrate for a given lecithin:cholesterol acyltransferase source. It is concluded that the frequently reported relationship between plasma cholesterol concentration and lecithin:cholesterol acyltransferase activity does not represent cause and effect. Also other variables influenced by bile-acid-sequestering agents, such as hepatic cholesterol synthesis, are unlikely to be major determinants of plasma lecithin: cholesterol acyltransferase activity.     

Plasma lecithin: cholesterol acyltransferase activity in liver disease

Abstract. In liver disease the proportion of plasma cholesterol present in the form of ester is lower than that found in normal subjects. Recent work has suggested that a plasma enzyme, lecithin: cholesterol acyltransferase (LCAT), may be a major f actorin the physiological regulation of plasma cholesterol ester levels. In patients with a variety of hepatobiliary disorders LCAT activity was found to be reduced and a study of the effects of interaction between normal and jaundiced plasmas supported the hypothesis that the low LCAT activity was due mainly to a reduction in the plasma concentration of the enzyme. When bile salts were added to an in vitro system clear evidence of inhibition of LCAT was produced only with concentrations higher than those normally found in the plasma of patients with liver disease. This casts doubt on the suggested role of bile salts as in vivo inhibitors of the enzyme. The cholesterol ester concentration of plasma showed good correlation with its LCAT activity when this was measured in a standard substrate. Our results suggest that reduction in LCAT activity may be an important factor in the production of the low ester: free ratio found in almost all hepatic disorders.     

Lecithin.cholesterol acyl-transferase and lipoprotein-X in liver disease

Determinations of serum lecithin : cholesterol acyl transferase (LCAT) and the “abnormal serum lipoprotein of cholestasis” (LP-X) have been carried out in 52 patients with different liver disorders and in 20 normal subjects.In acute hepatitis reduced LCAT activity was demonstrated in both LP-X positive and LP-X negative patients. In primary biliary cirrhosis and large bile duct obstruction the presence of LP-X was associated with reduced, normal or increased LCAT activity. Thus this study could reveal no specific LCAT/LP-X pattern in liver diseases, nor were we able to differentiate between intra- and extrahepatic cholestasis on the basis of these two tests.Possible relationships between LP-X and LCAT are discussed and mechanisms for the formation of LP-X in liver- and bile duct diseases are considered.     

Effect of lipoprotein concentration and lecithin: cholesterol acyltransferase activity on cholesterol esterification in human plasma after plasma exchange

The rate of cholesterol esterification in plasma, plasma lecithin cholesterol acyltransferase (LCAT) activity and plasma lipoprotein levels have been measured in five subjects who underwent therapeutic plasma exchange to reduce their plasma cholesterol concentration. In the week following the exchange the cholesterol esterification rate and the plasma triglyceride concentration returned rapidly in parallel to pre-exchange levels, while high density lipoprotein (HDL) cholesterol and LCAT activity returned to normal more slowly but also in parallel. The data suggest that the rate-limiting factor for cholesterol esterification in plasma is unlikely to be solely the enzyme levels, but is probably a combination of factors, including the enzyme level and either substrate availabiltiy or product removal. Plasma very low density lipoprotein (VLDL) may either provide substrates for the reaction or provide a means of removing one of the products from the site of reaction.     

A stable plasma lipoprotein and lecithin cholesterol acyltransferase control material

Fresh fasting plasma collected over EDTA was quick frozen and stored in liquid nitrogen. Ten aliquots were thawed over an 18-month period and phospholipids, cholesterol, triglycerides, lipoproteins and lecithin cholesterol acyltransferase were quantitated. There was no evidence that any of the parameters measured changed with time indicating that the plasma lipoproteins were stable. This method of preserving plasma lipoproteins is proposed as a means of obtaining reference materials that may be used to control day-to-day laboratory error and for comparison of methods between laboratories.     

Similar behaviour of lecithin:cholesterol acyltransferase and pseudocholinesterase in liver disease and hyperlipoproteinemia

Using exogenous substrate for its assay, lecithin:cholesterol acyltransferase (LCAT) was found to be decreased in liver disease and higher than normal in endogenous hypertriglyceridemia. LCAT activity was positively correlated with serum cholesterol and triglyceride. However in the six patients with excessive hypertriglyceridemia (type V), LCAT activity was lower than in type IV hyperlipoproteinemia. LCAT activity was not changed significantly in type II-a hyperlipoproteinemia. A striking parallel was noted between plasma LCAT and serum pseudocholinesterase activity. It suggested that both these liver secretion enzymes might be induced by an accelerated turnover of serum lipids and lipoproteins. Pathogenical implications of these findings are briefly discussed.     

Lack of association between plasma lecithin: cholesterol acyltransferase concentration and plasma sex hormone concentrations in men

Plasma lecithin:cholesterol acyltransferase (LCAT) concentration has been shown to be higher in women than in men, suggesting that sex hormones may influence LCAT metabolism. In order to explore this possibility, the associations of plasma LCAT concentration with the concentrations of total, free and protein-bound testosterone, 5 alpha-dihydrotestosterone and oestradiol in plasma, and with total androstenedione concentration in plasma, were examined in 88 men aged 52-67 yr. Total cortisol in plasma was also assayed. No statistically significant correlations were observed between LCAT and androgen or oestrogen concentrations, but a weak positive association was observed between LCAT and plasma cortisol concentration (r = +0.227, p less than 0.05).     

Effects of plasma infusion on plasma lipids, apoproteins and plasma enzyme activities in familial lecithin: cholesterol acyltransferase deficiency

Abstract. The siblings presented here are the third family found in Japan with familial LCAT deficiency. Their post-heparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured selectively by an immunochemical method. Plasma triglyceride levels were elevated, and post-heparin plasma lipoprotein lipase was decreased only in a patient with nephropathy, while hepatic triglyceride lipase activities were within reference limits in both patients. The plasma concentrations of apo A-I, apo A-II, and apo B were reduced in both patients. On the other hand, the plasma concentration of apo E was markedly increased. Enzyme replacement therapy by plasma transfusion in the propositus resulted in marked improvement of deranged compositions of triglyceride-rich lipoproteins. Also, improvement of the plasma apo E concentration was demonstrated, while the improvement of post-heparin lipase did not occur. These results suggest that LCAT may play an important physiological role in triglyceride metabolism as well as in cholesterol metabolism.     

Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level in patients with multiple sclerosis and evidence of direct synthesis in the brain

Summary Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated imapairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12±0.06 μg/ml (mean±SD) or about 2.2% of that in serum (5.4±1.4 μg/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2±2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06±0.02 μg/ml). Lipoprotein(a) concentration was below the sensitivity of the enzyme immunoassay used for the measurement (<40 ng/ml) in cerebrospinal fluid from both control subjects and those with demyelinating disease or multiple sclerosis.     

Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level in patients with multiple sclerosis and evidence of direct synthesis in the brain.

Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated impairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06 microgram/ml (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4 micrograms/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06 +/- 0.02 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.