Protein lipoprotein levels

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

Zairis MN, Ambrose JA, Manousakis SJ, et al. The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting the Global evaluation of new events and restenosis after stent implantation study. J Am Coll Cardiol 2002 40 1375-1382. 

Raloxifene (Evista) is a new SERM approved for use in the treatment and prevention of osteoporosis because it has estrogenic activity in bone. Raloxifene is an estrogen antagonist in both breast and endometrial tissues. The estrogenhke properties of raloxifene result in the maintenance of a favorable serum Upid profile (decreased low-density lipoprotein levels with no change in either high-density lipoproteins or triglycerides). Raloxifene is 95% bound to plasma proteins. Absorption of raloxifene is impaired by cholestyramine. 

Increased lipoprotein levels are seen in diabetes mellitus but not in starvation. Glucocorticoids have a protein catabolic activity in all tissues except liver. There, glucocorticoids stimulate protein synthesis. 

A better indication of a person s riidi of heart disease comes from a measurement of blood lipoprotein levels. Lipoproteins arc romfdex mol ecules with both lipid and protein parts that transport lipids through the body. They can be divided into four types ucconbiig to density as shown in 6tble 27.4. People with a high serum level high-density lipoproteins 4 HDL s) seem to have a decreased risk of heart disease. Asa rule of thumb, u person s risk drops about for each increase of 5 mg/dl.. in HDL con-... 

In summary, none of the above investigations have given any evidence of a primary abnormality in the production or utilization of serum proteins, lipoproteins, or glycoproteins. Also the feeding of amino acids (R19) or alterations in the protein level of the diet (Zl) do not change the disease process. 

Some people with elevated lipoprotein levels have VLDL that migrates on electrophoresis in the P band rather than the pre-p band (see Box 2-A). The presence of the P-VLDL is associated with a high incidence of artery disease, which is most likely to develop in persons homozygous for a genetic variant of apolipo-protein E. The problem may arise because apo-E is required for receptor-mediated uptake of VLDL, which interacfs both with tissue LDL receptors and with hepatic apo-E receptors. Genes for many of the... 

Hayek, T., Azrolan, N., Verdeny, R.B., Walsh, A., Shajek-Shaul, J., Agellon, L.B., Jail, A.R. and Breslow, J.L. (1993) Hypertension and cholesteryl ester transfer protein interact to dramatically alter high density lipoprotein levels, particle sizes and metabolism. Studies in transgemc mice. J. Clin. Invest. 92 1143-1152. 

Fenofibrate (propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate), a fibric acid derivative (Fig. 7.6), mainly exerts its effect via the activation of speciflc nuclear receptor called peroxisome proliferator-activated receptor alpha (PPARa). This PPARa agonist is primarily used to decrease the cholesterol levels in cardiovascular diseases patients. Like statins, fenofibrate also reduces triglycerides and low- and very low density protein levels. It also increases high-density lipoprotein levels in the body. Fenofibrate also has nonlipid (i.e., pleiotropic) effects (reduction in fibrinogen, C-reactive protein, and uric acid levels and improvement in the flow-mediated dilatation). 

A significant change in plasma lipoproteins has been reported by Olson after replacement of 75% of the total protein intake by carbohydrates. The ensuing hypolipoproteinemia involved primarily the LDL class. Resumption of normal protein intake resulted in a return to normal plasma lipoprotein levels. Similarly, Furman et al. (1959) reported that isocaloric substitution of carbohydrates for all dietary proteins produced a marked decrease of LDL. 

All serum Tipids, which consist of free cholesterol, glycerides, cholesterol ester and phospholipids, circulate in association with specific proteins (apo-lipoproteins) to form lipid-protein complexes. These macromolecular complexes are called "lipoproteins" and have remarkable hydrophilic properties, in spite of high lipid contents. Therefore, water insoluble lipids are transported from their organs for synthesis to their sites for utilization. Most serum lipoproteins have a molecular weight range from approximately 200,000 to 10,000,000 and contain from 40 % to 95 % of lipids. Studies of the factors affecting lipoprotein levels are very important for health and diseases, because lipoprotein levels are closely related to atherosclerosis and its clinical manifestations. 

Although the separation profile of the total lipoprotein fraction can be given by monitoring of protein moiety at A gg, the concentration of each lipoprotein class could not be calculated from peak area because of the difficulties in estimating lipoprotein levels caused by the following factors evaluation of turbidity, different molar coefficient of A2gg due to each lipoprotein, coelution of serum proteins with HDL fractions. At this point of view, a selective detection method of lipid components by enzymatic reaction using whole serum is useful for lipoprotein analysis as described in the next section. 

Mercer, N. J. H., Carroll, K. K., Wolfe, B. M., and Giovannetti, P. M., 1982, Plasma cholesterol, triglyceride, and lipoprotein levels in healthy adult volunteers when dietary milk protein was replaced by soy protein, Fed. Proc. (Abstr.) 41 531. 

In men with atherogenic dyslipemia of the insulin resistance syndrome, plasma C-reactive protein (CRP) levels showed positive correlations with body fat mass, waist girth, visceral adipose tissue, and insulin levels (measured in the fasting state and after a 75-g oral glucose load), but not with plasma lipoprotein levels (119). 

Inazu A, Brown ML, Hesler CB, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Eng J Med 1990 323 1234-1238. 

In this connection it is of interest that several other substances, known to interfere with protein synthesis, also cause fatty livers.Thus, administration of puromycin produces a fatty liver together with a decreased plasma lipoprotein level (Robinson and Seakins 1962). Orotic acid, which interferes with the normal formation of hepatic nucleotides and thus may affect protein synthesis, also causes fatty livers with low plasma lipoproteins (Standerfer and Handler 1955 Creasey et al. 1961). 

Results of animal experiments by Isselbacher et al. (1964) and by Sabesin et al. (1964) favor deficient synthesis of the protein moiety as a pathogenetic mechanism in a-j8-lipoproteinemia. When protein synthesis was inhibited in the rat by administration of puromycin, acetoxycycloheximide or ethionin, these authors found biochemical and morphological abnormalities which were very similar to those observed in a-j8-lipoproteinemia. The mucosal cells accumulated fat, serum triglycerides were low, and did not rise after fat loading, and the serum j8-lipoprotein level decreased precipitously. In these studies the dose of inhibitors was such that visible cell damage and a decrease in activation and esterification of fatty acids was not observed (Isselbacher 1965). 

Low density lipoprotein (LDL) (Section 26 11) A protein which cames cholesterol from the liver through the blood to the tissues Elevated LDL levels are a nsk factor for heart disease LDL is often called bad cholesterol... 

LIPOPROTEINS. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. 

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

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