Plasma lecithin-cholesterol acyltransferase

G7. Gjone, E., and Norum, K. R., Plasma lecithin-cholesterol acyltransferase and erythrocyte lipids in liver disease. Acta Med. Scand. 187, 153-161 (1970). 

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

G12. Glomset, J. A., Plasma lecithin cholesterol acyltransferase. In Blood Lipids and Lipoproteins (G. Nelson, ed.), pp. 745-787. Wiley, New York, 1972. 

Tl. Torsvik, H., Presence of ai-lipoprotein in patients with familial plasma lecithin cholesterol acyltransferase deficiency. Scand. J. Clin. Lab. Invest. 24, 187-196 (1969). 

A25. Aron, L, Jones, S., and Fielding, C. J., Human plasma lecithin cholesterol acyltransferase Characterization of cofactor-dependent phospholipase activity. J. Biol. Chem. 253, 7220-7226 (1978). 

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). 

K15. Kitabatake, K., Piran, U., Kamio, Y., Doi, Y., and Nishida, T., Purification of human plasma lecithin cholesterol acyltransferase and its specificity towards the acyl acceptor. Biochim. Biophys. Acta 573, 145-154 (1979). 

Nakamura Y., Kotite, L., Gan, Y., Spencer, T.A., Fielding C.J., Fielding P.E. 2004. Molecular mechanism of reverse cholesterol transport reaction of prebeta-migrating high density lipoprotein with plasma lecithin cholesterol acyltransferase. Biochemistry 43 14811-14820. 

Hitz, J., J. Steinmetz, and G. Siest. 1983. Plasma lecithin cholesterol acyltransferase—Reference values and effects of xenobiotics. Clinica ChimicaActa 133 85-96. 

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

Nakagawa M, Uchiyama M. 1974. Effect of organophosphate pesticides on lecithin-cholesterol acyltransferase in human plasma. Biochem Pharmacol 23 1641-1645. 

F2. Fielding, C. J., and Fielding, P. E., Purification and substrate specificity of lecithin-cholesterol acyltransferase from hiunan plasma. FEBS (Fed. Eur. Biochem. Soc.), Lett. 15, 355-358 (1971). 

F6. Forte, G. M., Norum, K. 11., Glomset, J. A., and Nichols, A. V., Plasma lipoproteins in familial lecithin cholesterol acyltransferase deficiency structure of low- and high-density lipoproteins as recorded by electron microscopy. J. Clin. Invest. 50, 1141-1148 (1971). 

Figure 21-1 Movement of triacylglycerols from liver and intestine to body cells and lipid carriers of blood. VLDL very low density lipoprotein which contains triacylglycerols, phospholipids, cholesterol, and apolipoproteins B, and C. IDL intermediate density lipoproteins found in human plasma. LDL low density lipoproteins which have lost most of their triacylglycerols. ApoB-100, etc., are apolipoproteins listed in Table 21-2. LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein (see Chapter 22).

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. 

ApoE is thought to reach the plasma from the liver in nascent HDL, diskshaped particles about 4.6-nm thick and with a mean diameter of about 19 nm which have clearly been shown to be of hepatic origin in the rat (H5). In plasma from human subjects with lecithin cholesterol acyltransferase deficiency a similar population of apoE-rich HDL particles, 14-40 nm in diameter and 4.4-4.5 nm thick, is seen (M37, S47). 

Origin and Plasma Concentration of 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). 

M27. Marcel, Y. L., and Vezina, C., Lecithin cholesterol acyltransferase of human plasma. J. Biol. Chem. 248, 8254-8259 (1973). 

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 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. 

Apolipoprotein A-I (ApoA-I) ApoA-I is the major protein component of HDL in plasma. The protein helps to clear cholesterol from arteries and promotes cholesterol efflux form tissues to the liver for excretion. It is a cofactor for lecithin cholesterol acyltransferase (LCAT), which is responsible for the formation of most plasma cholesteryl esters. 

Lipoproteins are often called pseudomicellar because their outer shell is in part composed of amphipathic phospholipid molecules. Unlike simple micelles, lipoproteins contain apolipoproteins, or apoproteins, in their outer shell and a hydrophobic core of triacylglycerol and cholesteryl esters. Unesterified, or free, cholesterol, which contains a polar group, can be found as a surface component and in the region between the core and surface (Figure 20-1). Most lipoproteins are spherical. However, newly secreted high-density lipoproteins (HDLs) from the liver or intestine are discoidal and require the action of lecithin-cholesterol acyltransferase (LCAT) in plasma to expand their core of neutral lipid and become spherical. The hydrophobic core of the low-density lipoprotein (LDL) molecule may contain two concentric layers one of triacylglycerol and another of cholesteryl ester. 

HDL High-density lipoprotein synthesized in the liver, the HDL serves as a source of apoUpoproteins for other lipoproteins, as the site of action for the conversion of cholesterol to cholesterol ester in the plasma by the enzyme lecithin-cholesterol acyltransferase (LCAT), and delivers cholesterol esters derived from peripheral membranes to the liver. It is commonly called the good cholesterol. ... 

---