Oleic acid cholesterol esters

There are a few reported cases of esterases that catalyze not only hydrolysis but also the reverse reaction of ester formation, in analogy with the global reaction described for serine peptidases (Fig. 3.4). Thus, cholesterol esterase can catalyze the esterification of oleic acid with cholesterol and, more importantly in our context, that of fatty acids with haloethanols [54], Esterification and transesterification reactions are also mediated by carboxyleste-rases, as discussed in greater detail in Sect. 7.4. 

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.

Lipid standards (2°/o solutions in chloroform) a triacylglycerol (triolein), cholesterol ester (cholesterol linoleate), fatty acid (palmitoleic, oleic, etc.), fatty acid methyl ester (linolenic acid, methyl ester), a glycerophosphatide (phosphatidylcholine, phosphatidylethano-lamine, etc.), a diacylglycerol (diolein), and a monoacylglycerol (monoolein). 

CRABP-GST is immobilized onto a glutathione-containing resin at a concentration that saturates the resin. A complex lipid mixture was prepared by combining a concentrated lipid extract derived from mouse tissue (brain) [5] (DMSO stock) with exogenously added retinoic acid (RA, positive control) and 13C-oleic acid (negative control). Analysis of this complex lipid mixture by LC-MS prior to incubation with immobilized CRABP demonstrated that the mixture contained RA (added), phospholipids, acylglycerols, cholesterol esters, and cholesterol. A portion of this mixture (corresponding to 1 nmol of RA) was added to PBS (DMSO concentration should not exceed 5%) and incubated with the CRABP-GST bound beads for 1 h. 

Cholesterol is formed in the liver (85%) and intestine (12%) - this constitutes 97% of the body s cholesterol synthesis of 3.2 mmol/day (= 1.25 g/day). Serum cholesterol is esterized to an extent of 70-80% with fatty acids (ca. 53% linolic acid, ca 23% oleic acid, ca 12% palmitic acid). The cholesterol pool (distributed in the liver, plasma and erythrocytes) is 5.16 mmol/day (= 2.0 g/day). Homocysteine stimulates the production of cholesterol in the liver cells as well as its subsequent secretion. Cholesterol may be removed from the pool by being channelled into the bile or, as VLDL and HDL particles, into the plasma. The key enzyme in the synthesis of cholesterol is hydroxy-methyl-glutaryl-CoA reductase (HGM-CoA reductase), which has a half-life of only 3 hours. Cholesterol is produced via the intermediate stages of mevalonate, squalene and lanosterol. Cholesterol esters are formed in the plasma by the linking of a lecithin fatty acid to free cholesterol (by means of LCAT) with the simultaneous release of lysolecithin. (s. figs. 3.8, 3.9) (s. tab. 3.8)... 

Among the simple lipids are also the cholesterol and cholesterol esters with acids such as palmitic, stearic, or oleic. These compounds are common compounds in most animal cells, although not in plants. Besides cholesterol, other zoosterols are known [la]. Several sterols are also present in plants (phytosterols), the most common being the sitosterol(s) and stigmasterol. 

The blood and tissues of animals typically contain not only unesterified cholesterol (UC), but also cholesterol esters (CE). Most of the CE are formed from long-chain fatty acids such as palmitic acid, oleic acid, linoleic acid, or arachidonic acid, but small amounts of cholesterol sulfate (CS) and cholesterol glucuronide also are present. The aim of this chapter is to provide a brief overview of the biochemistry, physiology, and pathology of these esters as an introduction to the field of CE research. The primary focus will be on long-chain fatty acid esters because much more is known about them than about other CE. However, current knowledge of the biochemistry of CS will be reviewed as well. 

Fatty acids and derivatives are abundant in biological membranes as components of phospholipids and cholesterol esters. In fact, their presence, in free or bound form, modulates the lipid membrane behaviour. It was demonstrated, with X-ray diffraction, that oleic acid produced important concentration-dependent alterations of the lipid membrane structure. Oleic acid is capable of altering markedly the phospholipid mesomorphism [79],... 

Unlike membranes where cholesterol is present in an unesterified form, only about 30% of the total serum cholesterol occurs as the free species, whereas the remaining 70% exists as cholesterol esters of long chain fatty acids, such as palmitic [CH3-(CH2)i4-COOH], stearic [CH3-(CH2)i6-COOH)], oleic [CH3-(CH2)7-CH=CH-(CH2)7=C00H)], linoleic [CH3-(CH2-CH=CH)3)=(CH2)7-C00H]. The hydrophobic character of long chain fatty acids is directly proportional to the number of carbon atoms in the chain [15]. Conversely, hydrophobicity in fatty acids containing the same number of carbon atoms decreases with the number of double bonds [15]. 

It has been reported that oleic acid is most readily esterified with cholesterol during its absorption (35, 34). Furthermore, Swell and Treadwell (34) also reported that the cholesterol ester which accumulated to the greatest extent, irrespective of the fatty acid fed, was cholesterol oleate. Thus, the endogenous cholesterol esters may be rich in oleic acid. 

The fatty acid spectrum of rice bran oil is 22-25% palmitic acid, 37-41% oleic acid and 37-41% linoleic acid. More recently, interest in rice oil escalated with its identification as a healthy oil that reduces serum cholesterol. Rice bran is a good source of antioxidants including vitamin E and oryzanol (ferulic esters of sterols and triterpene alcohols), cholesterol-lowering waxes and antitumor compounds like rice bran saccharide.Besides applications in nutrition and in phyto-chemicals, rice bran oil has traditionally been used for industrial applications, such as dimer acid manufacturing, depending on pricing for alternative vegetable oils. 

We propose the unsaturated lipids of biological membranes to provide the cells with an electronic conduction band. A striking feature of the unsaturated lipids in biomembranes is the very constant location of ethylenic cw-double bond in monounsaturated acyl chains between carbon atoms 9 and 10. A noteworthy exception is nervonic add (cw-15-24 1), which is abundant in central nervous system membranes. A microviscosity barrier has been observed in bilayers of dioleoylphosphatidylchohne at the depth of the oleic acid double bonds.Phospholipids belong to lyotropic liquid crystals and possess remarkable short- and long-range order. In a cell membrane lattice the local concentration of ester carbonyls and acyl chain ethylenic double bonds as well as the local concentration of cholesterol C=C bonds is very high. 

As with the male rat, the early reports that erucic acid somehow interfered with reproduction in the female rat are difficult to assess because the diets that were used may have been low in essential fatty acids (Carroll and Noble, 1957). Decreased numbers of pregnancies, resorption, and pseudopregnancies were observed in female rats fed diets supplemented with either erucic or oleic acids. Somewhat more plausible are the reports that the ovarian cholesterol content is increased in rats fed a HEAR oil containing diet (Carroll and Noble, 1952). When rats were fed ethyl erucate mixed with corn oil which is high in essential fatty acids, there were no noticeable reproductive abnormalities in the females (Walker eta/., 1972). As in the adrenal gland, the erucic acid in the ovaries accumulated as the cholesterol ester. Also, the cholesterol esters of 20 4 n-6, 22 4 n-6, and 24 1 n-9 were increased in the ovaries from these rats. An interesting observation by these authors was that rats fed an olive oil containing diet with no erucic acid accumulated appreciable quantities of esterified erucic acid, i.e., 3.1% of the cholesterol ester fraction and 1.4% of the phospholipid fraction. It was... 

Recently, oleic acid has been widely applied in phytosteryl esters(i.e., fatty acid (FA) ester forms of phytosterols), which are preferred in food formulations to overcome the problems of free forms of phytosterols since they possess very low solubility in edible oils and have a very high melting point (Contesini et al., 2013). Phytosterols are known to have a hypocholesterolemic effect, allowing the reduction of low-density lipoprotein cholesterol in plasma, whereas high-density lipoprotein cholesterol concentration is not affected by their consumption (Villeneuve et al., 2005). 

The role of linoleate in cholesterol deposition and transport is not entirely clear. Kelsey and Longenecker (1941) proved that 62% of the plasma cholesterol of cattle occurred in combination with linoleate. It is only natural to postulate that, in the absence of EFA, cholesterol is deposited in the liver, because there is insufficient linoleate available to transport it to other tissues for metabolism and excretion. However, it has been shown that, in such conditions, the increased cholesterol is deposited in the liver as an ester. The cholesterol esters in the liver of rats have been proved to consist almost entirely of those of saturated and oleic acids only approximately 10% of the cholesterol occurs in combination with linoleic acid, irrespective of whether or not the diet contains EFA (Achaya et al., 1954a). It would thus appear that Unoleic acid is of prime importance in the control of the distribution and deposition of cholesterol in the rat. Whether or not the same situation obtains in the case of man is a moot question. 

Palmitoleic acid and its ,3 homologue c/s-vaccenic acid (both n-1 monoene acids) have been reported to be inhibitors of mutagenesis and carcinogenesis (Hayatsu etal., 1988). Oral treatment with palmitoleic acid markedly prolonged the survival time of mice with Ehrlich ascites tumours, and the anti-tumour activity of palmitoleic acid is stronger than that of oleic acid (Ito et al., 1982). When palmitoleic acid-treated tumour cells were compared with control tumour cells, the total lipids and phospholipids contents were significantly lower and the fatty acid compositions of phosphatidylcholine, cholesterol esters, and triacylglycerols were considerably different (Ito et al., 1982). 

Cholesterol accumulated in atheromatous lesions is largely ester-ifled with fatty acids, especially oleic acid. The change in fatty acid composition of cholesterol esters between circulating lipoproteins and atheromas indicates an esterification process operative in the developing lesion. Kotharl et al have demonstrated enzymes in normal artery which catalyze both synthesis and hydrolysis of cholesterol esters. Reaction rates of esterification and hydrolysis were found to be strongly dependent on the physical state of the reactants an emulsified state promoted esterification, whereas a micellar state promoted hydrolysis. 

St. Clair et al. (1968) described the fatty acids synthesized from acetate by perfused pigeon aortas and incorporated into three lipid classes (phospholipids, glycerides, cholesteryl esters). The major newly synthesized fatty acids were stearic acid in the phospholipid fraction stearic, palmitic, and oleic acids in the glycerides and oleic acid in the cholesteryl esters. The synthesis of all the fatty acids in all the lipid classes was increased in the atherosclerotic aortas. Especially noteworthy was the finding that the synthesis of oleic acid and its esterification to cholesterol was stimulated to the greatest extent. 

A deficiency of essential fatty acids or, vice versa, a relative oversupply of saturated fatty acids [203, 204] has been suggested as an aetiologic factor. Indeed it has been shown that the fatty acid composition of brain [105, 206] or its mitochondria [207] can be altered by varying the levels of unsaturated fatty acids in the diet. However, in the PE fraction of MS white matter which harbours the greatest concentration of PUFA, their proportion is increased [134, 208]. Only the PC fraction containing a small proportion of dienes and a minimal one of arachidonic acid showed values of dienes lower than in the controls in three of seven of MS fractions [134] and in another series [208] a reduction of arachidonic acid. Yet in MS myelin [134] the ratio of essential fatty acids was similar to that in the controls. The deficit of oleic acid reported for the serum cholesterol esters and triglycerides correlates to the status of the patient and increases with the progress of the disease. It is not reflected in the fatty acids of the phospholipids [193]. Thus, the data available do not appear to support the assumption of an essential fatty acid deficiency. 

The major forms of vitamin A (apart from carotene) are the esters of retinol with long chain fatty acids. Compared with the normal pattern of fatty acids in tissue lipids, they are a relatively select group and much more saturated. Palmitic acid predominates, together with smaller quantities of stearic and oleic acids. When the esters reach the lumen of the small intestine, they are almost completely hydrolysed, absorbed into the intestinal cells and reesterified. They are transported as components of the chylomicrons to the liver where they are stored almost entirely as retinyl palmitate, regardless of the composition of the dietary esters. Modification of dietary retinyl esters to such a specific fatty acid composition requires, as in the case of the cholesterol esters, specific hydrolytic and synthetic enzymes. These occur mainly in the liver, intestine and the retina of the eye. 

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