Plasma 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). 

A) The activity of plasma lecithin cholesterol acyltransferase (LCAT) is increased. 

M31 Miller, J. P. Failure of orotic acid to suppress activity of plasma lecithin cholesterol acyltransferase. Scand. J. Clin. Lab. Invest., 38 138-141 (1978)... 

Lecithin xholesterol acyltransferase antioxidant activity prevented the formation of oxidised lipids during lipoprotein oxidation (Vohl etal. 1999). Once minimally oxidised LDL is present, it inhibits plasma lecithin xholesterol acyltransferase activity and thereby impairs HDL metaboUsm and reverse cholesterol transport (Holvoet etal. 1998, Bie-LiCKi and Forte 1999). 

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. 

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. 

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. 

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. 

Cholesteryl esters arise from the activity of acyl-CoA-cholesterol acyltransferase which catalyzes the formation of the esters from acyl-CoA and cholesterol, and also from the activity of lecithin-cholesterol acyltransferase (LCAT) that catalyzes the formation of the ester from a fatty acyl group on phosphatidyl choline. The first enzyme is cytoplasmic while the second one is associated with HDL in blood plasma. 

The esterification of cholesterol in animals has attracted considerable research because of the possible involvement of cholesterol and its ester in various disease states (cf. Glomset and Norum, 1973, and Sections 12.1, 12.3 and 12.6). Cholesterol esters are formed by the action of lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43) which is particularly active in plasma (cf. Sabine, 1977, for a review of cholesterol metabolism). The reaction involves transfer of a fatty acid from position 2 of lecithin (phosphatidylcholine) to the 3-hydroxyl group of cholesterol with the formation of monoacyl-phosphatidylcholine. Although LCAT esterifies plasma cholesterol solely at the interface of high-density lipoprotein and very-low-density lipoprotein, the cholesterol esters are transferred to other lipoproteins by a particular transport protein (CETP cholesteryl ester transfer protein). Cholesteryl esters, in contrast to free cholesterol, are taken up by cells mostly via specific receptor pathways (Brown et aL, 1981), are hydrolysed by lysosomal enzymes and eventually re-esterified and stored within cells. LCAT may also participate in the movement of cholesterol out of cells by esterifying excess cholesterol in the intravascular circulation (cf. Marcel, 1982). 

One interesting property of FED plasma is its poor capacity to activate cholesterol esterification [6]. Specifically it will not activate the formation of cholesterol esters in HDL, but it will do so in other lipoproteins. FED plasma lacks, therefore, a-HDL lecithin cholesterol acyltransferase (LCAT), although p-LCAT is present in normal amounts. 

Esterification of cholesterol When cholesterol is taken up by HDL, it is immediately esterified by the plasma enzyme phos-phatidylcholine cholesterol acyltransferase (PCAT, also known as LCAT, in which "L" stands for lecithin). This enzyme is synthesized by the liver. PCAT binds to nascent HDLs, and is activated by apo A-l. PCAT transfers the fatty acid from carbon 2 of phosphatidyl-... 

Chronic parenchymal liver disease is associated with relatively predictable changes in plasma lipids and lipoproteins. Some of these changes are related to a reduction in the activity of lethicin cholesterol acyltransferase (LCAT). This plasma enzyme is synthesized and glycosylated in the liver then enters the blood, where it catalyzes the transfer of a fatty acid from the 2-position of lecithin to the Sp-OH group of free cholesterol to produce cholesterol ester and lysolecithin. As expected, in severe parenchymal liver disease, in which LCAT activity is decreased, plasma levels of cholesterol ester are reduced and free cholesterol levels normal or increased. 

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