Cholesterol esterification

Chiesa G, Michelagnoli S, Cassinotti M, Gianfranceschi G, Werba JP, Paz-zucconi F, et al. Mechanisms of high-density lipoprotein reduction after probu-col treatment changes in plasma cholesterol esterification/transfer and lipase activities. Metabolism 1993 42 229-235. 

De Medina P, Payre BL, Bernad J, Bosser I, Pipy B, Silvente-Poirot S, Favre G, Faye JC, Poirot M (2004b) Tamoxifen is a potent inhibitor of cholesterol esterification and prevents the formation of foam cells. J Pharmacol Exp Ther 308 1165-1173... 

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). 

Cholesterol metabolism. Hydrogenated oil, administered orally to hamsters at a dose of 20% of diet for 4 weeks, induced hypercholesterolemia. Oil feeding had no effect on cholesterol synthesis but markedly inhibited cholesterol esterification in both the liver and the intestine. The diet-induced hypercholesterolemia was strongly correlated with an increase in acyl-CoA/cholesterol acyltransferase activity. The hypercholesterolemia increased aortic uptake of cholesterol and hence acyl-CoA/cholesterol acyltransferase activity " Coconut fat, administered orally to rabbits with partial ileal bypass, produced a significant increase of serum total cholesterol and phospholipids concentrations. The effect on semm lipids of the type of fat was similar in control and partial ileal bypass rabbits A Coconut—a main source of energy for two... 

Pentchev PG, Comly ME, Kruth HS, Vanier MT, Wenger DA, Patel S, Brady RO (1985) A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci U S A 82 8247-8251... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

LCAT acts preferentially on lipids transported by HDL (so-called a-LCAT activity), but also on lipids transported by apoB-containing lipoproteins (so-called jS-LCAT activity) [58, 85]. In practice, LCAT activity is measured either as the activity required to esterify radioactive cholesterol that has been exogenously incorporated into native HDL or into artificial HDL-like particles (a-LCAT activity) or which has been equilibrated with endogenous lipoproteins of the plasma sample (cholesterol esterification rate, CER) [21, 58, 85]. Several variations of these assays have been reported, some of which are available as commercial test kits (e.g., Roar Biomedical, New York, USA). In addition, LCAT concentration can be determined by either laboratory-made tests or by a commercial ELISA kits [57]. However, the decrease in LCAT concentration is difficult to judge since it also decreases secondary to HDL deficiency due to causes other than LCAT deficiency. Plasma from patients with LCAT deficiency fails to esterify radioactive cholesterol provided by any substrate. By contrast, plasmas of patients with fish-eye disease show a near-normal cholesterol ester-fication rate but have a selective inability to esterify radioactive cholesterol provided to plasma with native HDL or reconstituted HDL (a-LCAT activity) [58, 85]. 

Patients with classical LCAT deficiency fail to esterify cholesterol in any substrate and hence have both an undetectable or very low cholesterol esterification rate and a-LCAT activity. Patients with fish-eye disease usually have a normal cholesterol esterification rate and a selective a-LCAT deficiency. 

The two significant sources of cholesterol in body are endogenously synthesized cholesterol and exogenous or dietary cholesterol. Efforts to inhibit the absorption of dietary cholesterol have primarily focused on the inhibition of ACAT, a major enzyme associated with cholesterol esterification. Inhibition of this enzyme blocks the absorption of intestinal cholesterol and may also inhibit cholesteryl ester deposition in the vascular wall in the form of fatty streaks associated with atherosclerotic plaque. 

Debry P, Nash EA, Neklason DW, Metherall JE. 1997. Role of multidrug resistance p-glycoproteins in cholesterol esterification. J Biol Chem 272 1026-1031. 

Steinmetz A, Hocke G, Saile R, Puchois P, Fruchart JC. Influence of serum amyloid A on cholesterol esterification in human plasma. Biochim Biophys Acta 1989 1006 173-178. 

VL Meiner, S Cases, HM Myers, ER Sande, S Bellosta, M Schambelan, RE Pitas, J McGuire, J Herz, RV Farese Jr. Disruption of the acyl-CoAxholesterol acyltransferase gene in mice evidence suggesting multiple cholesterol esterification enzymes in mammals. Proc Natl Acad Sci (USA) 93 14041-14046, 1996. 

I Tabas, X Zha, N Beatini, JN Myers, FR Maxfield. The actin cytoskeleton is important for the stimulation of cholesterol esterification by atherogenic lipoproteins in macrophages. J Biol Chem 269 22547-22556, 1994. 

The rate of cholesterol esterification in plasma is not correlated with HDL concentration (A12, R17, S45, S58, Wl, W2) but is correlated with the concentration of VLDL or triglyceride (A12, P8, R17, S58, T7, Wl, W2). Although HDL is the major substrate for LCAT, VLDL and indirectly LDL are the major recipients of the esterfied cholesterol, transferred (it is thought) by lipid transfer protein. Accumulation of esterified cholesterol in the recipient lipoproteins is associated with a decrease in LCAT activity (C7, Fll, F13) that can be relieved by the addition of recipient lipoproteins but not by addition of LCAT substrate (Fll). Hopkins and Barter (H32, H33) have explained these observations by showing that the depletion of HDL esterified cholesterol by transfer to VLDL enhances the capacity of HDL to act as a substrate for LCAT. 

A12. Albers, J. J., Chen, C.-H., and Adolphson, J. L., Lecithimcholesterol acyltransferase (LCAT) mass its relationship to LCAT activity and cholesterol esterification rate. /. Lipid Res. 22, 1206-1213 (1981). 

Bll. Barter, P. J., Hopkins, G. J., Corjatschko, L., and Jones, M. E., Competitive inhibition of plasma cholesterol esterification by human high density lipoprotein-subfraction 2. Biochim. Biophys. Acta 793, 260-268 (1984). 

G9. Glomset, J. A., The mechanism of the plasma cholesterol esterification reaction Plasma fatty acid transferase. Biochim. Biophys. Acta 65, 128-135 (1962). 

Ihm, J., Ellsworth, J. L., Chataing, B., and Harmony, J. A. K., Plasma protein-facilitated coupled exchange of phosphatidylcholine and cholesteryl ester in the absence of cholesterol esterification. ]. Biol. Chem. 257, 4818-4827 (1982). 

P8. Patsch, W., Lisch, H. J., Sailer, S., and Braunsteiner, H., Initial cholesterol esterification rate in hyperlipoproteinemia Effects of triglyceride-rich lipoproteins. Eur. J. Clin. Invest. 8, 209-213 (1978). 

P13. Pinon, J. C., Bridoux, A. M., and Laudat, M. H., Initial rate of cholesterol esterification associated with high density lipoproteins in human plasma. /. Lipid Res. 21, 406-414 (1980). 

P23. Poorthuis, B. J. H. M., and Wirtz, K. W. A., Increased cholesterol esterification in rat liver microsomes by purified non-specific phospholipid transfer protein. Biochim. Biophys. Acta 710, 99-105 (1982). 

Soloff, L. A., and Varma, K. G., Relationship between high density lipoproteins and the rate of in vitro serum cholesterol esterification. Scand. J. Clin. Lab. Invest. 38 (Suppl. 150), 72-76 (1978). 

Sugano, M., and Portman, O. W., Fatty acid specificities and rates of cholesterol esterification in vivo and in vitro. Arch. Biochem. Biofihys. 107, 341-351 (1964). 

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). 

Ross, A.C., Rowe, J.F. 1984. Cholesterol esterification by mammary gland microsomes from the lactating rat. Proc. Soc. Exper. Biol. Med. 176, 42-47. 

HMG-CoA reductase, a rate-limiting enzyme of cholesterol synthesis, and ACAT-1, a rate-limiting enzyme of cholesterol esterification, relate to hepatic cholesterol storage. Levels of mRNA of those enzymes were also increased by the lipodystrophy model diet during the onset of hepatic steatosis, but DHA supplementation attenuated this (Fig. 22.6). 

Vidal, R., Hemandez-Vallejo, S., Pauquai, T, Texier, O., Rousset, M., Chambaz, J., Demignot, S., Lacorte, J. M. (2005). Apple procyanidins decrease cholesterol esterification and lipoprotein secretion in Caco-2/TC7 enterocytes. J. Lipid Res., 46, 258-268. 

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