Cholesteryl ester structure

Qiu X, Mistry A, Ammirati MJ et al (2007) Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules. Nat Struct Mol Biol 14 106-113... 

Figure 2S-1. Generalized structure of a plasma lipoprotein. The similarities with the structure of the plasma membrane are to be noted. Small amounts of cholesteryl ester and triacylglycerol are to be found in the surface layer and a little free cholesterol in the core.

Loading of guests within the SCKs (for potential delivery) is modeled after lipoproteins, which are composites of cholesterol, cholesteryl ester, phospholipids, and protein forming biological structures of core-shell morphology... 

Tabata N, Tomoda H, Omura S (1999) Ferroverdins, Inhibitors of Cholesteryl Ester Transfer Protein Produced by Streptomyces sp. WK-5344. II. Structure Elucidation. J Antibiotics 52 1108... 

Most plasma cholesterol is in an esterified form (with a fatty add attached at C-3, see Figure 18.2), which makes the structure sen more hydrophobic than free cholesterol. Cholesteryl esters are rot found in membranes, and are normally present only in low levels in most cells. Because of their hydrophobicity, cholesterol and ils esters must be transported in association with protein as a compo nent of a lipoprotein particle (see p. 225) or be solubilized by phos pholipids and bile salts in the bile (see p. 223). 

Regulation of the LDL receptor gene involves a hormone-response element (HRE, see p. 238).] Third, if the cholesterol is not required immediately for some structural or synthetic purpose, it is esterified by acyl CoA cholesterol acyltransferase (ACAT, AC AT transfers a fatty acid from a fatty acyl CoA derivative to cholesterol, producing a cholesteryl ester that can be stored in the cell (Figure 18.21). The activity of ACAT is enhanced in the presence of increased intracellular cholesterol. 

Many larger lipid carrier proteins are known. The 476-residue plasma cholesteryl ester transfer protein is discussed briefly in Chapter 22. Plasma phospholipid transfer proteins are of similar size.t/U A 456-residue human phospholipid-binding protein interacts with the lipopolysaccharide of the surfaces of gram-negative bacteria (Fig. 8-30) and participates in the immune response to the bacteria. It has an elongated boomerang shape with two cavities, both of which bind a molecule of phosphatidylcholine. Other plasma lipid transfer proteins may have similar structures/... 

The structures of the various lipoproteins appear to be similar (figs. 20.11 and 20.12). Each of the lipoprotein classes contains a neutral lipid core composed of triacylglycerol and/or cholesteryl ester. Around this core is a coat of protein, phospholipid, and cholesterol, with the polar portions oriented toward the surface of the lipoprotein and the hydro-phobic parts associated with the neutral lipid core. The hydrophilic surface interacts with water in plasma, promoting the solubility of the lipoprotein. 

There are at least nine apoproteins associated with the lipoproteins, as well as several enzymes and a cholesteryl ester transfer protein. There are two major types of apoproteins. Two apoproteins (apo B100 and apo B48) are tightly integrated into the phospholipid monolayer. The other seven proteins are less tightly associated with the phospholipid and exchange among the lipoproteins. The apoproteins have three major functions. (1) They are important structural components. (2) Some of the apoproteins modulate the ac-... 

Tomoda H, Matsushima C, Tabata N, Namatame I, Tanaka H, Bamberger MJ, Arai H, Fukazawa M, Inoue K, Omura S (1999) Structure-Specific Inhibition of Cholesteryl Ester Transfer Protein by Azaphilones. J Antibiot 52 160... 

Free fatty acids, derived primarily from adipocyte triglycerides, are transported as a physical complex with plasma albumin. Triglycerides and cholesteryl esters are transported in the core of plasma lipoproteins [134], Deliconstantinos observed the physical state of the Na+/K+-ATPase lipid microenvironment as it changed from a liquid-crystalline form to a gel phase [135], The studies concerning the albumin-cholesterol complex, its behavior, and its role in the structure of biomembranes provided important new clues as to the role of this fascinating molecule in normal and pathological states [135]. 

H Tomoda, C Matsushima, N Tabata, I Namatame, H Tanaka, H Arai, M Fukazawa, K Inoue, S Omura. Structure-specific inhibition of cholesteryl ester transfer protein by azaphilones. J Antibiot 52 160-170, 1999. 

N Tabata, H Tomoda, S Omura. Erabulenols A and B, inhibitors of cholesteryl ester transfer protein, produced by Penicillium sp. FO-5637. II. Structure elucidation of erabulenols A and B. J Antibiot 51 624-628, 1998. 

MZ Kuo, RJ Zielinski, JI Cialdella, CK Marschke, MJ Dupui s, GP Li, DA Klooster-man, CH Spilman, VP Marshall. Discovery, isolation, structure elucidation and biosynthesis of U-106305, a cholesteryl ester transfer protein inhibitor from UC11136. J Am Chem Soc 117 10629-10634, 1995. 

In summary, therefore, one can say that the core of lipoprotein particles is disordered (or liquid) at body temperature, with the partial exception of some LDL and HDLX containing a high proportion of saturated cholesteryl esters. The biological implications of lipoprotein core structure are unknown. 

ACAT transfers amino-acyl groups from one molecule to another. ACAT is an important enzyme in bile acid synthesis, and catalyses the intracellular esterification of cholesterol and formation of cholesteryl esters. ACAT-mediated esterification of cholesterol limits its solubility in the cell membrane and thus promotes accumulation of cholesterol ester in the fat droplets within the cytoplasm this process is important in preventing the toxic accumulation of free cholesterol that would otherwise damage ceU-membrane structure and function. Most of the cholesterol absorbed during intestinal transport undergoes ACAT-mediated esterification before incorporation into chylomicrons. In the liver, ACAT-mediated esterification of cholesterol is involved in the production and release of apo-B-containing lipoproteins. 

The topic of lipoproteins is the most complicated issue presented in this chapter. Lipoproteins are complexes of specific proteins and lipids. Each lipoprotein contains different proportions of various lipids. The constant component of any one type of lipoprotein is the protein hence, the structure or function is described by first naming the protein. Lipoproteins are synthesized primarily in the intestines and liver and are secreted into the plasma, where their function is to transport various Lipids. Lipoproteins are water soluble because of their outside coat of proteins and the hydrophilic phosphate groups of their phospholipids. This water solubility enables lipoproteins to transport the triglycerides and cholesteryl esters that reside within their cores. An understanding of lipoproteins is useful to individuals interested in energy metabolism and essential to those concerned with cardiovascular disease. 

---