Lecithin:cholesterol acyltransferase, activity

GIO. Gjone, E., Blomhoff, I. P., and Wienecke, I., Plasma lecithin cholesterol acyltransferase activity in acute hepatitis. Scand. J. Gastroenterol. 6, 161-168 (1971). 

E5. Ellerbe, P., and Rose, H. G., Dependence of human plasma lecithin cholesterol acyltransferase activity upon high density lipoprotein2. Biochim. Biophys. Acta 713, 670-674 (1982). 

Fll. Fielding, C. J., and Fielding, P. E., Regulation of human plasma lecithin cholesterol acyltransferase activity by lipoprotein acceptor cholesteryl ester content. J. Biol. Chem. 256, 2102-2104 (1981). 

T7. Thanabalasingham, S., Thompson, G. R., Trayner, T. I., Myant, N. B., and Soutar, A. K., Effect of lipoprotein concentration and lecithin cholesterol acyltransferase activity on cholesterol esterification in human plasma after plasma exchange. Eur. J. Clin. Invest. 10, 45-48 (1980). 

Castro, G., Nihoul, L., Dengremont, C., Geitere, C., Delfly, B., Tailleux, A., Fievet, C., Duverger, N., Denefle, R, Fruchart, J.-C., and Rubin, E. (1997). Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-p particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry 36, 2243-2249. 

Parks JS, Thuren TY, Schmitt JD. Inhibition of lecithin cholesterol acyltransferase activity by synthetic phosphatidylcholine species containing eicosapentaenoic acid or docosahexaenoic acid in the sn-2 position. J Lipid Res 1992 33 879-887. 

Carlson LA, Holmquist L (1985) Evidence for deficiency of high-density lipoprotein lecithin-cholesterol acyltransferase activity (a-LCAT) in Fish Eye disease. Acta Med Scand 218 189-196... 

ApoC-I is expressed mainly in liver but also in lung, skin, testis, spleen, neural retina, and RPE. Its multiple functions include the activation of lecithin cholesterol acyltransferase (LCAT) and the inhibition, among others, of lipoprotein and hepatic lipases that hydrolyze triglycerides in particle cores. Notably, both LCAT and lipoprotein lipases are expressed in RPE and choroid (Li et al., 2006). Moreover ApoC-I has been shown to displace ApoE on the VLDL and LDL and thus hinder their binding and uptake via their corresponding receptors (Li et al., 2006). 

The best-known effect of APOE is the regulation of lipid metabolism (see Fig. 10.13). APOE is a constituent of TG-rich chylomicrons, VLDL particles and their remnants, and a subclass of HDL. In addition to its role in the transport of cholesterol and the metabolism of lipoprotein particles, APOE can be involved in many other physiological and pathological processes, including immunoregu-lation, nerve regeneration, activation of lipolytic enzymes (hepatic lipase, lipoprotein lipase, lecithin cholesterol acyltransferase), ligand for several cell receptors, neuronal homeostasis, and tissue repair (488,490). APOE is essential... 

Funke H, Eckardstein A von, Pritchard PH, Albers JJ, Kastelein JJ, Droste C, Assmann G (1991) A molecular defect causing fish eye disease an amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity. Proc Natl Acad Sci U S A 88 4855-4859... 

Steinmetz A, Utermann G. Activation of lecithin Cholesterol acyltransferase by human apolipoprotein A-IV. J Biol Chem. 1985, 260 2258-2264. 

Chen CH, Albers JJ. Activation of lecithin Cholesterol acyltransferase by apolipopro-teins E-2, E-3, and A-IV isolated from human plasma. Biochim Biophys Acta. 1985, 836 279-285. 

Hyperlipidemia (mainly hypercholesterolemia) is a regular part of nephrotic syndrome (K13, W6). Serum levels of cholesterol are often markedly elevated, usually above 10 mmol/L. However, in severely malnourished patients, normal or even decreased serum cholesterol level can be found. Serum levels of triacylglyc-erols fluctuate, from normal values to markedly elevated values (mainly in patients with proteinuria higher than 10 g/24 hr). There is a variable increase in plasma concentrations of very low density lipoproteins (VLDL, they correlate negatively with serum albumin level), intermediate-density lipoproteins (IDL), andLDL however, plasma concentrations of HDL are usually normal (J3). Levels of lipoprotein(a) [Lp(a)j are also increased (W4). Remission of nephrotic syndrome or decrease of proteinuria may result in the decrease of plasma concentrations of Lp(a) (G2). Concentration of free fatty acids in serum is commonly decreased because they are normally bound to albumin and albumin is lost into the urine. The activity of lecithin cholesterol acyltransferase (LCAT) is usually decreased. 

Apolipoproteins serve to direct metabolism of particular lipoproteins by acting as cofactors or perhaps inhibitors for enzymes. Examples are apoA-I and apoC-I, each of which may activate lecithin cholesterol acyltransferase... 

A16. Albers, J. J., Lin, J., and Roberts, G. P., Effect ofhuman plasma apolipoproteins on the activity of purified lecithin cholesterol acyltransferase. Artery 5, 61-75 (1979). 

A few words about HDL these lipoproteins are synthesized largely by the liver. They act as ApoE, ApoC, and ApoA traffickers, but in addition, they also serve as a factory for the synthesis of cholesterol esters. HDL may absorb free cholesterol from various peripheral tissues, including arteries. Cholesterol is then converted to a large extent to fatty acyl esters by the action of the enzyme lecithin-cholesterol acyltransferase [LCAT see Equation 19.2)]. LCAT is activated by ApoA-I. Inactive LCAT is a plasma component. 

Cholesterylesters arise from the activity of acyl-CoA cholesterol acyltransferase, which catalyzes the formation of the esters from acyl-CoA, and also from the activity of lecithin cholesterol acyltransferase, which catalyzes the formation of the ester from phosphatidylcholine. 

HDLs gradually accumulate cholesteryl esters, converting nascent HDLs to HDL2 and HDL3. Any free cholesterol present in chylomicron remnants and VLDL remnants (IDLs) can be esterifled through the action of the HDL-associated enzyme, lecithin cholesterol acyltransferase (LCAT). LCAT is synthesised in the liver and so named because it transfers a fatty acid from the C-2 position of lecithin to the C-3-OH of cholesterol, generating a cholesteryl ester and lysolecithin. The activity of LCAT requires interaction with apo-A-I, which is found on the surface of HDLs. 

The liver synthesizes two enzymes involved in intra-plasmic lipid metabolism hepatic triglyceride lipase (HTL) and lecithin-cholesterol-acyltransferase (LCAT). The liver is further involved in the modification of circulatory lipoproteins as the site of synthesis for cholesterol-ester transfer protein (CETP). Free fatty acids are in general potentially toxic to the liver cell. Therefore they are immobilized by being bound to the intrinsic hepatic fatty acid-binding protein (hFABP) in the cytosol. The activity of this protein is stimulated by oestrogens and inhibited by testosterone. Peripheral lipoprotein lipase (LPL), which is required for the regulation of lipid metabolism, is synthesized in the endothelial cells (mainly in the fatty tissue and musculature). 

Lecithin-cholesterol acyltransferase is a water-soluble plasma enzyme that plays an important role in the metabolism of HDLs by catalyzing the formation of cholesteryl esters on HDLs through the transfer of fatty acids from the sn-2 position of phosphatidylcholine to cholesterol (Jonas, 1986). ApoA-1 is the major cofactor of LCAT in HDLs and reconstituted lipoproteins (Fielding et ai, 1972). Many laboratories have used techniques such as synthetic peptide analogs (Anantharamaiah et ai, 1990a Anantharamaiah, 1986), monoclonal antibodies (Banka et al., 1990), and recombinant HDL particles (Jonas and Kranovich, 1978) to attempt to identify the major LCAT-activating region of apoA-I. 

Terpenic compounds are resorbed from the digestive tract and sue situated in the hepatie tissues. Thanks to their ability to dissolve fats, they prevent the formation of cholesterol gathering inside the liver and they also recover proper colloidal state to the bile. Terpenes also enhance the bile content in the hepatic cells and in the liver tracts. Terpenic hydrocarbons dilating the smooth muscles [78, 79] make the hepatic tracts more distended both inside and outside. It has been pointed out that the terpenes contained in Rowachol dissolve bile stones [87-89]. The meehanism of terpenes activity has not as yet been completely explained. It was explained that menthol and other monoterpenes inhibit the activity of the lecithin-cholesterol acyltransferase in the human serum [90]. They also lower the activity of the hepatic S-3-hydroxy-3-methylglutaryl-CoA reductase, which is responsible for the physiological inhibition of cholesterol synthesis in the liver [82, 91, 92]. 

There are currently no published data regarding EL mass or activity levels in human plasma. Indeed, there has been relatively little study of phosphohpase activity in human plasma. Phospholipase activity increases after administration of heparin [24]. Some of the phospholipase activity in human plasma [25] has been attributed to lecithin-cholesterol acyltransferase (LCAT) [26] and hepatic lipase [27]. In the presence of inflammation, the secretory phospholipase A2 (sPLA2) may account for some of the plasma phosphohpase achvity and is also increased after heparin administration [28]. The contribuhon of endofhehal hpase to plasma phospholipase activity is unknown, but fhe decrease in post-heparin phosphohpase activity in EL knockout mice suggests that EL may contribute substantiaUy to plasma phosphohpase activity in humans. 

The hypertriglyceridemia of renal failure resembles the endogenous familial variety, and may likewise coexist with insulin resistance, glucose intolerance, and hyperuricemia. In dialysis patients it is associated with a high rate of coronary artery disease in women and white men under 60 years (C26). The low HDL cholesterol levels, found mainly in white men on hemodialysis, are attributed to decreased activity of the enzyme lecithin cholesterol acyltransferase (L-CAT). Decreased enzyme activator apo-apo A1 and inhibitory uremic toxins have been proposed as causes for the decreased enzyme activity. Low HDL cholesterol levels are associated with an increased risk of atherosclerotic heart disease (C26). 

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