Cholesterol efficiency

Other Addition Reactions.—A quantitative study of the epoxidation of 3-substituted cholest-5-enes with peroxy-acid shows that both the rate and the epimer ratio vary according to the C(3)-substituent. " The epoxidation clearly has some electrophilic character. o-Sulpho-perbenzoic acid, which may be used in aqueous-organic solvents, converted cholesterol efficiently into the a-epoxide (89%). The A -olefinic bond in cholestan-5,16-dien-3 -ol is sufficiently reactive, perhaps as a consequence of ring strain, to permit selective 16a, 17a-epoxidation. " ... 

The imprinted j8-CyD polymers, prepared with the use of cholesterol as the template, bound cholesterol in water far more efficiently than did the polymer obtained in the absence of the template. The effect of molecular imprinting is evident. Cholesterol is too large to be accommodated in the cavity of one -CyD molecule. Thus, two (or more) )8-CyD molecules must simultaneously interact with one cholesterol molecule in order to bind cholesterol efficiently. Only when the molecular imprinting method is used and several )8-CyD molecules are placed in the desired positions, eminent and practically useful polymeric receptors can be obtained. 

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Zarzycki and coworkers [77] studied the influence of temperature on the separation of cholesterol and bile acids using reversed-phase stationary phases. The best chromatographic conditions for the separation of mnlticomponent samples of steroids were chosen. Experiments were performed on wettable plates with RP-18W and at the temperatnres of 5, 10, 20, 30, 40, 50, and 60°C. The studies showed (Figure 9.9) that the degree of separation in the high-temperature region can be increased by an improvement of the efficiency of the chromatographic system. However, a relatively weak retention-temperatnre response for the studied steroids was observed. 

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). 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Recent data indicate that SR-BI is a nonspecific receptor for many lipophilic molecules (Lorenzi et al., 2008 Reboul et al., 2007b). Apart from HDLs, rodent SR-BI also binds to LDL, VLDL, acetylated LDL, oxidized LDL, and maleylated bovine serum albumin. SR-BII has a similar ligand specificity and function to that of SR-BI (Webb et al., 1998). However, it has been shown that vitamin E (which like carotenoids is carried in the bloodstream mainly by LDL and HDL) is transported more efficiently into the endothelial cells from HDLs than from LDLs (Balazs et al., 2004 Kaempf-Rotzoll et al., 2003 Mardones and Rigotti, 2004). This is in striking contrast to cholesterol, which is taken up much more efficiently from LDLs than HDLs by the RPE to the retina (Tserentsoodol et al., 2006b). It remains to be shown which lipoproteins are the main carriers for carotenoids transported from blood into the RPE. 

A new cholesterol flow injection analysis biosensor has also been described as an application of the H2O2 ECL sensor56. In that work, the luminol electrochemiluminescence, previously studied in aqueous media, was implemented in Veronal buffer added of 0.3% triton X-100 (v/v), 0.3% PEG and 0.4% cholate to enable the solubilisation of the cholesterol and then its efficient oxidation catalyzed by the immobilized cholesterol oxidase. The ECL reaction occurred thus in a micellar medium and the performances of the H2O2 ECL sensor were investigated. 

C-labelled cholesterol was used to test the recovery of 5-100 pg of faecal sterols from seawater (labelled coprostanol not being available). The radioactivity of the samples and eluates was measured by a two-channel liquid scintillation counter. Percentage recovery was calculated on the basis of the amount of labeled material recovered in the acetone eluant. The results indicate that column extraction efficiency is not adversely affected by the salinity of the water samples, i.e., in the range 95-97%. 

The rare example of synergistic action of a binary mixture of 1-naphthyl-A-phcnylaminc and phenol (1-naphthol, 2-(l,l-dimethylethyl)hydroquinone) on the initiated oxidation of cholesterol esters was evidenced by Vardanyan [34]. The mixture of two antioxidants was proved to terminate more chains than both inhibitors can do separately ( > /[xj). For example, 1-naphtol in a concentration of 5 x 10 5 mol L-1 creates the induction period t=170s, 1 -naphthyl-A-phenylamine in a concentration of 1.0 x 10-4 mol L 1 creates the induction period t = 400s, and together both antioxidants create the induction period r = 770 s (oxidation of ester of pelargonic acid cholesterol at 7= 348 K with AIBN as initiator). Hence, the ratio fs/ZfjXi was found equal to 2.78. The formation of an efficient intermediate inhibitor as a result of interaction of intermediate free radicals formed from phenol and amine was postulated. This inhibitor was proved to be produced by the interaction of oxidation products of phenol and amine. 

Extracellular ligands (hormones, neurotrophins, carrier protein, adhesion molecules, small molecules, etc.) will bind to specific transmembrane receptors. This binding of specific ligand induces the concentration of the receptor in coated pits and internalization via clathrin-coated vesicles. One of the best studied and characterized examples of RME is the internalization of cholesterol by mammalian cells [69]. In the nervous system, there are a plethora of different membrane receptors that bind extracellular molecules, including neurotrophins, hormones and other cell modulators, being the best studied examples. This type of clathrin-mediated endocytosis is an amazingly efficient process, capable of concentrating... 

Activators and inhibitors regulate not the amount of enzyme protein but the activity ( efficiency ) of that which is present. Two principal mechanisms of control are (i) competitive and (ii) allosteric. Competitive control (inhibition) occurs when a compound which is structurally similar to the true substrate binds to the active site of the enzyme. This is how a number of drugs and poisons bring about their effect. For example, a group of therapeutic drugs called statins are used to treat heart disease because by inhibiting a key enzyme called HMGCoA reductase, they reduce the hepatic synthesis of cholesterol and therefore the plasma concentration of that lipid. 

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