Lecithin:cholesterol acyl transferase

DAG diacylglycerol LCAT lecithin-cholesterol acyl transferase... 

Clandra, S., Margin, M. J., and McIntyre, N., Plasma lecithin cholesterol acyl-transferase activity in liver disease. Eur. J. Clin. Invest. 1, 352-360 (1971). 

Peelman F, Vandekerckhove J, Rosseneu M (2000) Structure and function of lecithin cholesterol acyl transferase new insights from structural predictions and animal models. Curr Opin Lipidol 11 155-160... 

The fourth major lipoprotein type, high-density lipoprotein (HDL), originates in the liver and small intestine as small, protein-rich particles that contain relatively little cholesterol and no cholesteryl esters (Fig. 21-40). HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins (Table 21-3), as well as the enzyme lecithin-cholesterol acyl transferase (LCAT), which catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol (Fig. 21-41). LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of chylomicron and VLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped nascent HDL to a mature, spherical HDL particle. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded some of this cholesterol is converted to bile salts. 

FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT). This enzyme is present on the surface of HDL and is stimulated by the HDL component apoA-I. Cholesteryl esters accumulate within nascent HDLs, converting them to mature HDLs. 

The plasma lipoproteins contain eight major apoproteins, the structure and function of which have recently been reviewed (5). Briefly, the primary amino acid sequence is known for five of these apoproteins. ApoB, a highly hydrophobic protein, is found in chylomicrons, VLDL and LDL. It is the major polypeptide in LDL and has been shown to be responsible, in part, for the recognition of LDL by its receptor in cultured human fibroblasts (7,10). The major polypeptides of HDL are apoA-I and apoA-II apoA-l activates lecithin cholesterol acyl transferase. In addition, studies on the cellular level suggest that apoA-I may regulate the content of the lipids in the cell membrane (8). 

The metabolism of HDL probably involves interaction with both hepatic and peripheral cells, as well as with other lipoproteins. HDL may remove cholesterol from tissues, the "scavenger hypothesis (11,12). The cholesterol may then be esterifed by the action of lecithin cholesterol acyl transferase. HDL may provide cholesterol to the liver for bile acid synthesis (13) and some HDL may be catabolized by the liver in the process. HDL has not been found to interfere with the binding of LDL in cultured human fibroblasts (6). However, in cultured human arterial cells, porcine or rat hepatocytes, and rat adrenal gland, there appears to be some competition of HDL with LDL binding sites, suggesting the presence of a "lipoprotein-binding" site (14). 

A low Km reflects a high affinity for the substrate, and a high Km, a low affinity. Lecithin-cholesterol acyl transferase is a transferase it transfers the fatty acyl group from lecithin to cholesterol. 

Mechanisms of Exercise-Induced Changes in Plasma Lipids Lipoprotein Lipase, Hepatic Triglyceride Lipase and Lecithin Cholesterol Acyl Transferase... 

Figure 2. Proposed yet speculative mechanism by which hlgh-denslty lipoprotein (HDL) increases in response to exercise via decreased hepatic lipase activity. Lecithin cholesterol acyl transferase (LCAT).

The rate-limiting step for cholesterol synthesis is the production of mevalonate from 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) by the enzyme HMG-CoA reductase. Cholesterol synthesised in the hep-atocyte can be further metabolised by lecithin cholesterol acyl transferase (LCAT) to cholesterol ester, which is packaged into lipoproteins and secreted into the bloodstream. Alternatively, it can be excreted via the biliary system either as a neutral lipid or following conversion to bile acids. 

HDL and LCAT. While all this is going on, there is a scavenger called HDL which carries unwanted, excess cholesterol, partly from cell breakdown, back to the liver (largely within LDL remnants) where the cholesterol might end up being excreted (for instance, as bile salts). LCAT (lecithin-cholesterol acyl transferase) is an enzyme associated with HDL that reesterifies free cholesterol. 

D. HDL removes cholesterol from cell membranes. The lecithin cholesterol acyl transferase (LCAT) reaction, which converts the cholesterol to cholesterol esters, occurs on HDL. 

M. Rosseneu. A proposed architecture for lecithin cholesterol acyl transferase (LCAT) identification of the catalytic triad and molecular modeling. Protein Sci. 1998, 7, 587-599. 

FIGURE 9.1 Simplified overview of lipid and lipoprotein metabolism with some key enzymes numbered (1) cholesteryl ester transfer protein (CETP), (2) hepatic triglyceride lipase, (3) lecithin cholesterol acyl transferase (LCAT), and (4) lipoprotein lipase. 

Bile acids inhibit plasma lecithin cholesterol acyl transferase (LCAT) cf. 224), the activity of which is low in obstructive jaundice and in diseases with impaired liver function cf 224,225). However, it has been pointed out that the serum bile acid concentrations found in patients with obstructive... 

Goyal, J., Wang, K., Liu, M., Subbaiah, P.V. Novel function of lecithin cholesterol acyl-transferase.1997 272 16231-9. 

Lecithin Cholesterol Acyl Transferase, Cholesterol Ester Exchange/Transfer Protein, and Lipoprotein Particles... 

More than 80% of the cholesteryl esters (CE) found in human plasma derive from the reaction of lecithin cholesterol acyl transferase (LCAT). Since the content of CE in plasma high positively correlates with the incidence of atherosclerosis and myocardial infarction, there has been in the past and still is great interest in investigation of the enzymes involved in lipoprotein metabolism. This overview summarizes some general features, with particular emphasis on investigations carried out in our laboratory (a) the substrates of LCAT in plasma (b), the influence of LCAT on the Upoprotein spectrum (c) the distribution of formed CE after the action of LCAT (d) the impact of cholesteryl ester transfer/exchange protein (CETP) on Upoprotein metabolism. 

Further reading Gjone, E., Norum, K.R. and Glomset, J.A. (1978). Familial lecithin cholesterol acyl transferase deficiency. In Stanbury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease, 4th Edn., p. 589. (New York McGraw-Hill)... 

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