Cholesterol in plasma

Patients with classical LCAT deficiency show an increased proportion of unesterified cholesterol in plasma (80-100%). By contrast, the plasma from patients with fish-eye disease has a slightly elevated proportion of unesterified cholesterol (up to 70%). 

Dobiasova M, Frohlich J (1996) Measurement of fractional esterification rate of cholesterol in plasma depleted of apoprotein containing lipoprotein methods and normal values. Physiol... 

The HMG-CoA reductase inhibitors (Statins like simvastatin, lovastatin, pravastatin, fluvastatin, etc.) inhibit the enzyme and thereby decrease the hepatic cholesterol synthesis and increase the synthesis of LDL receptors causing increased clearance of LDL and a reduced concentration of LDL cholesterol in plasma. HMG-CoA reductase inhibitors are used to treat elevated LDL which also causes a small reduction in plasma triglycerides and an increase in HDL cholesterol. 

Familial hypercholesterolemia (FH) (common) is characterised by elevation of total and LDL-cholesterol in plasma. In the more severe heterozygous form, this affects about 1 500 of the population (one copy of the LDL-receptor protein is absent or defective). LDL-cholesterol is elevated from childhood. Untreated, half the males will be dead by 60 years, females 10 years later. The principal consequence is coronary heart, but occasionally also peripheral and cerebrovascular disease. 

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Chn Chem 1972 18 499-502. 

Role of HDL in peripheral cholesterol removal. Free cholesterol in plasma membranes of peripheral tissues is transferred to apo A-I containing pre-/ -HDL (nascent HDL), via an ATP-binding cassette transporter 1 (ABCl). Cholesterol is esterified by LCAT and stored in the core of the HDL particle. In the presence of suitable acceptor lipoproteins (VLDL or LDL), cholesteryl esters are transferred from HDL via apo D and CETP to the lower density lipoproteins, thereby shortening the half-life of plasma cholesterol since VLDL and LDL have a much faster turnover time than HDL. PL = Phospholipid. 

Familial apolipoproteinA-Iand C-IIIdeficiency is characterized by mild comeal opacification, coronary artery disease, marked HDL deficiency, and a normal ratio of free cholesterol to esterified cholesterol in plasma in all probands, also yellow orange, lipid-laden plaques on the tmnk, eyelids, neck, chest, anus, and backs of several affected individuals. The LDL is often found to be triacylglycerol-rich. The mode of inheritance is autosomal codominant. 

LDL receptors and thus increased clearance of LDL-cholesterol in plasma [44,45]. 

Cholesterol travels in the bloodstream via lipoprotein complexes called Chylomicrons, VLDL, IDL, LDL, and HDL. Of the five lipoprotein classes, LDL is by far the richest in cholesterol. Cholesterol in plasma lipoproteins exists both as the free sterol and esterified at its hydroxyl position with a long-chain fatty acid, usually unsaturated (see also Table 18.1). The LDL particle contains a single molecule of apoprotein B-lOO (Mr = 513,000) as its primary protein component. Because cholesterol biosynthesis is confined primarily to the liver with some occurring also in intestine, LDL plays an important role in delivering cholesterol to other tissues. Cholesterol esters are too hydrophobic to traverse cell membranes by themselves and must be transported into cells via specialized LDL receptors. 

Excess cellular cholesterol in plasma membranes, or cholesterol released from the breakdown of cells, enters another type of lipoprotein, high-density lipoprotein (HDL). 

Osono, Y., Woollett, L.A., Marotti, K.R., Melchior, G.W., and Dietschy, J.M. (1996) Centripetal Cholesterol Flux from Ex-trahepatic Organs to the Liver Is Independent of the Concentration of High Density Lipoprotein-Cholesterol in Plasma, Proc. Natl. Acad. Sci. USA 93,4114 119. 

Much evidence has accrued for a role for inflammation in atherosclerosis. One of the most dramatic demonstrations of this role was the observation in the early 1960s that in cholesterol-fed rabbits given cortisone, no raised lesions developed in spite of higher levels of cholesterol in plasma and in the arterial wall... 

Friedewald, W.T., Levy, R.I., and Fredrickson, D.S. (1972) Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge, Clin. Chem. 18,499-502. 

Eder, K., U. KeUer, and C. Brandsch. 2004. Effects of a dietary oxidized fat on cholesterol in plasma and lipoproteins and the susceptibihty of low-density lipoproteins to hpid peroxidation in guinea pigs fed diets with different concentrations of vitamins E and C. International. Jounml for Vitamin and Nutrition Research 74 11-20. 

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). 

Miura, M. Gomyo, T. Effect of melanoidin on cholesterol in plasma, liver and feces in rats fed a high-cholesterol diet. In The Maillard Reaction in Food Processing, Human Nutrition and Physiology , Finot, P.A. Aesch-bacher, H.U. Hurrel, R.F. Liardon, R., Eds. Birkhauser Verlag Basel, 1990 pp 291—296. 

Low density lipoproteins (LDL). Lipoproteins with buoyant density 1.006-1.063 g/mL that carry most of the cholesterol in plasma. LDL infiltrates the inner part of the artery wall and contribute cholesterol to enlarging atherosclerotic plaques. 

Figure 7.9 shows the relationship between the concentration of cholesterol (section 4.3.1.3) in plasma, and specifically cholesterol in plasma low-density lipoproteins (LDL section 5.6.2.2), and premature death from ischaemic heart disease. The main dietary factor affecting the concentration of cholesterol in plasma is the intake of fat. 

Free and esterified cholesterol can be measured during the determination of a total lipid profile by the methods described in Chapter 8 (Section I). On the other hand, so important is the absolute concentration of cholesterol in plasma as a diagnostic marker in disease states believed to be that a number of methods have been developed for the rapid determination of cholesterol alone by various means. For routine clinical applications, all such methods, including GC, should be capable of a high degree of automation. The procedures available have been reviewed and compared elsewhere [336,659, 1011], Enzymatic and colorimetric methods appear to be favoured in most routine clinical applications... 

The doubling of mg% cholesterol in plasma (Table 1) shows that the 3 fractions were active. The values for uric acid suggest that the activity was not due to toxic tissue destruction. The apparent greater potency of anterior fraction H was not seen with the lower dose at which no extract was active. 

Rabbit Mg% Cholesterol in Plasma, Hours After Injection of UA ... 

Sphingomyelin (SM) A Hpid with a phosphocholine group linked to a ceramide shares the same head group as phosphatidylcholine (PC) but displays different physicochemical properties. SM and PC do not normally mix in biological membranes, because SM is associated with cholesterol in plasma membrane microdomains such as lipid rafts. 

Metabolism Changes in tissue fatty acid composition Cholesterol in plasma i Cholesterol in liver adrenals skin f Mitochondria swelling and uncoupling of oxidative phosphorylation Liver triacylglycerol output ... 

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