Cholesterol, methyl

Total sterols cholesterol 24-methyl cholesterol sitosterol ... 

The side chains shown in Tables 20.8 and 20.9 are of the conventional type (cholesterol, 24-methyl- and 24-methyl-enecholesterol, with or without additional unsaturation at position 22), or similar to those of dinosterol, 23-demethylgorgosterol or gorgosterol. 

Figure 2. Mixed monolayers of cholesterol- methyl palmitate system at 27° C. and pH 6...

We are now in a position to examine the various systems listed in Table I which follow Type I behavior. Experimentally (Figure 2) the behavior of the cholesterol-methyl palmitate system shows excellent agreement with the generalized system depicted in Figures 12 and 13,... 

If cholesterol esters are esterified directly and the free cholesterol is not removed prior to GC analysis, it may dehydrate to form cholestadiene on the column and this may obscure some of the C22 components [499]. Similarly, cholestadiene and cholesterol methyl ether are generated to some extent when most acidic reagents are used for transesterification, and analogous by-products are formed from plant sterols [376,494,626,835]. This does not occur with base-catalysed transesterification. Other hydrolysis products of low molecular weight from lipids, such as phytol and aldehydes, can be troublesome in some... 

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Synthetic chemical approaches to the preparation of carbon-14 labeled materials iavolve a number of basic building blocks prepared from barium [ CJ-carbonate (2). These are carbon [ C]-dioxide [ CJ-acetjlene [U— C]-ben2ene, where U = uniformly labeled [1- and 2- C]-sodium acetate, [ C]-methyl iodide, [ C]-methanol, sodium [ C]-cyanide, and [ CJ-urea. Many compHcated radiotracers are synthesized from these materials. Some examples are [l- C]-8,ll,14-eicosatrienoic acid [3435-80-1] inoxn. [ CJ-carbon dioxide, [ting-U— C]-phenyhsothiocyanate [77590-93-3] ftom [ " CJ-acetjlene, [7- " C]-norepinephrine [18155-53-8] from [l- " C]-acetic acid, [4- " C]-cholesterol [1976-77-8] from [ " CJ-methyl iodide, [l- " C]-glucose [4005-41-8] from sodium [ " C]-cyanide, and [2- " C]-uracil [626-07-3] [27017-27-2] from [ " C]-urea. All syntheses of the basic radioactive building blocks have been described (4). 

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

Ketone body synthesis occurs only in the mitochondrial matrix. The reactions responsible for the formation of ketone bodies are shown in Figure 24.28. The first reaction—the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA—is catalyzed by thiolase, which is also known as acetoacetyl-CoA thiolase or acetyl-CoA acetyltransferase. This is the same enzyme that carries out the thiolase reaction in /3-oxidation, but here it runs in reverse. The second reaction adds another molecule of acetyl-CoA to give (i-hydroxy-(i-methyl-glutaryl-CoA, commonly abbreviated HMG-CoA. These two mitochondrial matrix reactions are analogous to the first two steps in cholesterol biosynthesis, a cytosolic process, as we shall see in Chapter 25. HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction. This reaction is mechanistically similar to the reverse of the citrate synthase reaction in the TCA cycle. A membrane-bound enzyme, /3-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to /3-hydroxybutyrate. 

The methyl ester and benzyl ester forms can be used as a rubefacient (a vasodilator that opens up capillaries, which as a side effect makes the skin redden). It also works to reduce plasma cholesterol. 

The cis P-lactams 57 are shown to act as cholesterol absorption inhibitors <96BMCL1947> and 58, an analogue of the dipeptide Phe-Gly methyl ester, is a protease inhibitor <96BMCL983>. A straightforward synthesis of proclavaminic acid 59, a biosynthetic precursor of clavulanic acid, is reported <96TA2277>. 

Step 5—Formation of Cholesterol The formation of cholesterol from lanosterol takes place in the membranes of the endoplasmic reticulum and involves changes in the steroid nucleus and side chain (Figure 26-3). The methyl groups on C,4 and C4 are removed to form 14-desmethyl lanosterol and then zymosterol. The double bond at 03—C9 is subsequently moved to Cj-Cg in two steps, forming desmosterol. Finally, the double bond of the side chain is reduced, producing cholesterol. The exact order in which the steps described actually take place is not known with certainty. 

Cholesterol is synthesized in the body entirely from acetyl-CoA. Three molecules of acetyl-CoA form mevalonate via the important regulatory reaction for the pathway, catalyzed by HMG-CoA reductase. Next, a five-carbon isoprenoid unit is formed, and six of these condense to form squalene. Squalene undergoes cychzation to form the parent steroid lanos-terol, which, after the loss of three methyl groups, forms cholesterol. 

PARKER R A, PEARCE B 0, CLARK R w, GORDON D A, WRIGHT J J (1993) Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy 3-methyl-glutaryl-coenzyme A reductase. J Biol Chem, 268 11230-38. 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

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