Lecithin cholesterol acyltransferase

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

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

Lysolecithin (lysophosphatidylcholine) may be formed by an alternative route that involves lecithin cholesterol acyltransferase (LCAT). This enzyme. 

FIGURE 9. Endogenous lipoprotein metabolism. In liver cells, cholesterol and triglycerides are packaged into VLDL particles and exported into blood where VLDL is converted to IDL. Intermediate-density lipoprotein can be either cleared by hepatic LDL receptors or further metabolized to LDL. LDL can be cleared by hepatic LDL receptors or can enter the arterial wall, contributing to atherosclerosis. Acetyl CoA, acetyl coenzyme A Apo, apolipoprotein C, cholesterol CE, cholesterol ester FA, fatty acid HL, hepatic lipase HMG CoA, 3-hydroxy-3-methyglutaryl coenzyme A IDL, intermediate-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LDL, low-density lipoprotein LPL, lipoprotein lipase VLDL, very low-density lipoprotein. 

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). 

A7. Albers, J. J., Taggart, H, M., Applebaum-Bowden, D., Haffner, S., Chesnut, C. H., Ill, and Hazzard, W. R., Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid Stanozolole. Biochim. Biophys. Acta 795, 293-296 (1984). 

LCAT, lecithin cholesterol acyltransferase CETP, cholesterol ester transfer protein SR-61, scavenger receptor-BI... 

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... 

Figure 11.15 The reaction catalysed by lecithin cholesterol acyltransferase (LCAT). LinoLeate is transferred from a phospholipid in the blood to cholesterol to form cholesteryl linoleate, catalysed by LCAT. The cholesterol ester forms the core of HDL, which transfers cholesterol to the liver. Discoidal HDL (i.e. HDL3) is secreted by the liver and collects cholesterol from the peripheral tissues, especially endothellial cells (see Figure 22.10). Cholesterol is then esterified with lin-oleic acid and HDL changes its structure (HDL2) to a more stable form as shown in the lower part of the figure. R is linoleate.

The HDLs also originate in the liver. They return the excess cholesterol formed in the tissues to the liver. While it is being transported, cholesterol is acylated by lecithin cholesterol acyltransferase (LCAT). The cholesterol esters formed are no longer amphipathic and can be transported in the core of the lipoproteins. In addition, HDLs promote chylomicron and VLDL turnover by exchanging lipids and apoproteins with them (see above). 

Phosphatidylcholine-sterol acyltransferase— lecithin-cholesterol acyltransferase (LCAT) ... 

A2. Akanuma, Y., and Glomset, J., A method for studying the interaction between lecithin cholesterol acyltransferase and high density lipoproteins. Biochem. Bio-phys. Res. Commun. 32, 639-643 (1968). 

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). 

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. 

H5. Ho, W. K. K., and Nichols, A. V., Interaction of lecithin cholesterol acyltransferase with sonicated dispersions of lecithin. Biochim. Biophys. Acta 231, 185-193 (1971). 

Simon, J. B., and Scheig, R., Serum cholesterol esterification in liver disease. Importance of lecithin-cholesterol acyltransferase. New Engl. J. Med. 283,841-846 (1970). 

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). 

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