Erythrocyte, cholesterol

Erythrocytes Cholesterol Phosphatidylcholine Phosphatidylethanolamine Phosphatidylserine Phosphatidyl nositol Sphingomyeline 40% 00%... 

Table 7.4. Erythrocyte Cholesterol in Various Common Mammals (Nelson, 1967)...

Several studies, in part contradictory, are available concerning the influence of nicotinic acid on cholesterol biosynthesis. Perry (1960) reported from work with rat liver slices a decreased incorporation of C-acetate into cholesterol with high concentrations of nicotinic acid in the medium Schade and Saltman (1959) had obtained similar results in rabbits fed with nicotinic acid. On the other hand, Merrill and Lemley-Stone (1957) found increased cholesterol synthesis in liver slices of rats fed nicotinic acid, while Duncan and Best (1960) reported that nicotinic acid has no effect on C-acetate incorporation. Parsons (1961 a) studied the effects of nicotinic acid and niacin on incorporation of C-acetate in man, and stated that considerably less conversion into serum cholesterol (free and esterifled) and into erythrocyte cholesterol occurred during nicotinic acid administration. The concept of inhibition of cholesterol synthesis is also held by Goldsmith (1962) the point of inhibition supposedly occurs before the formation of squalene, because sterol intermediates between squalene and cholesterol could not be detected in serum. 

Cholesterol is found in many biological membrane and is the main sterol of animal organisms. It is eqnimolar with phospholipids in membranes of liver cell, erythrocytes, and myelin, whereas in human stratum comeum it lies in the outermost layer of the epidermis... 

Lysolecithins act by dissolving cholesterol and cause massive losses of the sterol from membranes (19). Lysolecithins have been shown to cause the formation of openings 300-400 A in diameter in erythrocyte plasma membranes (20). Unlike saponins, lysolecithin membrane openings are permanent. 

Brydon and Roberts- added hemolyzed blood to unhemolyzed plasma, analyzed the specimens for a variety of constituents and then compared the values with those in the unhemolyzed plasma (B28). The following procedures were considered unaffected by hemolysis (up to 1 g/100 ml hemoglobin) urea (diacetyl monoxime) carbon dioxide content (phe-nolphthalein complex) iron binding capacity cholesterol (ferric chloride) creatinine (alkaline picrate) uric acid (phosphotungstate reduction) alkaline phosphatase (4-nitrophenyl phosphate) 5 -nucleotidase (adenosine monophosphate-nickel) and tartrate-labile acid phosphatase (phenyl phosphate). In Table 2 are shown those assays where increases were observed. The hemolysis used in these studies was equivalent to that produced by the breakdown of about 15 X 10 erythrocytes. In the bromocresol green albumin method it has been reported that for every 100 mg of hemoglobin/100 ml serum, the apparent albumin concentration is increased by 100 mg/100 ml (D12). Hemolysis releases some amino acids, such as histidine, into the plasma (Alb). 

G7. Gjone, E., and Norum, K. R., Plasma lecithin-cholesterol acyltransferase and erythrocyte lipids in liver disease. Acta Med. Scand. 187, 153-161 (1970). 

Samples are injected (1 pi) using the splitless mode, and helium is used as a carrier gas with an inlet pressure of 2.5 Bar (250 kPa). The temperature programme starts at 50°C and is maintained for 1.5 min, followed by an increase to 190°C at a rate of 30°C/min. After holding the temperature at this level for 5 min, the gradient continues at a rate of 8°C/min until a final level of 230°C. This will be sufficiently maintained to allow all high-boiling substances (cholesterol ) to be eluted. The total analysis time will be approximately 45 min. An example of a chromatogram of control erythrocytes is shown in Fig. 3.3.2. 

In 1925, E. Gorter and F. Grendel (J. Exp. Med. 41, 439) reported measurements in which they extracted lipid from red blood cell membranes with acetone, spread the lipids as a monolayer, and measured the area of the compressed monolayer. They then estimated the surface area of an erythrocyte and calculated that the ratio of the lipids (as a monolayer) to the surface area of the red blood cell was 1.9-2.0. More modern experiments gave the following each erythrocyte membrane contains 4.5 x 10 16 mol of phospholipid and 3.1 x 10-16 mol of cholesterol. 

Some studies have shown increased risks of violent death and depression in subjects with reduced serum cholesterol concentrations. Serum and membrane cholesterol concentrations, the microviscosity of erythrocyte membranes, and platelet serotonin uptake have been determined in 17 patients with hypercholesterolemia (21). There was a significant increase in serotonin transporter activity only during the first month of simvastatin therapy. This suggests that within this period some patients could be vulnerable to depression, violence, or suicide. This is an important paper, in that it explains why mood disorders are not regularly seen in clinical trials with statins, as has been summarized in a recent review (3). 

Cholesterol - an essential component of mammalian cells - is important for the fluidity of membranes. With a single hydroxy group, cholesterol is only weakly am-phipathic. This can lead to its specific orientation within the phospholipid structure. Its influence on membrane fluidity has been studied most extensively in erythrocytes. It was found that increasing the cholesterol content restricts molecular motion in the hydrophobic portion of the membrane lipid bilayer. As the cholesterol content of membranes changes with age, this may affect drug transport and hence drug treatment. In lipid bilayers, there is an upper limit to the amount of cholesterol that can be taken up. The solubility limit has been determined by X-ray diffraction and is... 

The effect of organophosphorous insecticides such as methylbromfenvinfos on membrane fluidity has been studied using the fluorescence anisotropy of 1,6-diphenyl-l,3,5-hexatriene (DPH), a probe known to be located in the hydrophobic core of the bilayer, and 1,3-bis (1-pyrene) propane (Py(3)Py), a probe distributed in the outer layer region [54]. DPH revealed a broadening of the transition profile and a solidifying effect in the fluid phase of DMPC and DPPC in the presence of 50 pM insecticide. An ordering effect of the insecticide in the fluid state was revealed by Py(3)Py. In addition, the pretransition in DPPC and DMPC vesicles was abolished by the insecticide. The addition of cholesterol decreased the influence of the insecticide. It was also observed that the influence on native membranes (erythrocytes, lymphocytes, brain microsomes, and sarcoplasmic reticulum) depended on the cholesterol content of the membranes. 

Interaction and adhesion of biological surfaces are central considerations for other physiological conditions as well. Platelets, erythrocytes, the vascular endothelium and other tissues interact during thrombosis and hemostasis. Also, when erythrocytes come in contact with artificial surfaces, damage often occurs and blood trauma may result. Finally, the accumulation of cholesterol deposits on the interior walls of arteries is responsible for atherosclerosis. 

Cholesterol Human Erythrocyte 25 Bovine Erythrocyte 30 Human Platelet 22... 

As one further explores the chemical and compositional nature of the phospholipids in cells, some very interesting comparisons can be made, admittedly using a broad brush. The distribution of lipids (including cholesterol), human erythrocytes (red blood cells), bovine erythrocytes, and human platelets serve as good examples. This information is provided in Table 1-4. 

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