Lipoprotein types

The fourth major lipoprotein type, high-density lipoprotein (HDL), originates in the liver and small intestine as small, protein-rich particles that contain relatively little cholesterol and no cholesteryl esters (Fig. 21-40). HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins (Table 21-3), as well as the enzyme lecithin-cholesterol acyl transferase (LCAT), which catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol (Fig. 21-41). LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of chylomicron and VLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped nascent HDL to a mature, spherical HDL particle. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded some of this cholesterol is converted to bile salts. 

Type Lipoprotein type increased Serum triglyceride Serum cholesterol... 

Lipoprotein Type Drag of Choice Combination Therapy... 

E. Multiple lipoprotein-type hyperlipidemia (Type Ila, Ilb or IV pattern). Elevated LDL, possibly due to excess production of VLDL. There is premature atherosclerosis. 

Table 6.6 gives compositions for several of the lipoprotein types that have been discussed in this chapter. The high TG contents of chylomicrons 80-95%) and VLDLs 55-65%) are consistent with their function in distributing this eneigy-rich nutrient to various tissues. The low TG content of HDLs implies that these parti cles arc not used to supply energy to cells. 

Several studies have shown that PMN production of cytokines during microbial stimulation requires activation of MAPK. Using specific MAPK inhibitors, neutrophil IL-8 production in response to LPS, Mycoplasma fermentans membrane lipoproteins, type III group B streptococci, as well as TNF-a and GM-CSF was found to be dependent upon p38 MAPK [22-24,33]. The ERKl/2 and p38 MAPK are also involved in LPS andM. fermentans membrane lipoprotein-stimulated IL-8 production, as determined by inhibitor studies with PD98059 and SB203580 [22]. 

The measurement of the uptake kinetics indicated that high-density lipoprotein might be the primary source of the vitamin E uptake by type II pneumocytes (Kolleck et al. 1999). Vitamin E depletion of rats caused an increase of vitamin E uptake by isolated type II pneumocytes from high-density hpoprotein but not from low-density lipoprotein or very low-density lipoprotein. Type II pneumocytes express the scavenger receptor class B type 1 (SR-Bl), a high-density lipoprotein-specific receptor. Vitamin E depletion caused an increased expression of SR-Bl by a post-transcriptional mechanism. The increased vitamin E uptake from high-density lipoprotein and the increased expression of the SR-Bl were reversed by refeeding the vitamin. 

Combined Effects of Bioactive Compounds in Lipid Profile Recruiting Hyperlipidemia low-density-lipoprotein-type elevated triglycerides Dietary supplement Armolipid Plus Dietary supplement placebo... 

Lipoprotein type Density (kg/l) Triacylglycerols (%) Cholesterol/its esters %) Phospholipids (%) Proteins (%)... 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Lipoprotein formed by hydrolysis of triglycerides in VLDL elevated in type III hyperlipoproteinemia. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

The concentration of total protein in human plasma is approximately 7.0-7.5 g/dL and comprises the major part of the solids of the plasma. The proteins of the plasma are actually a complex mixture that includes not only simple proteins but also conjugated proteins such as glycoproteins and various types of lipoproteins. Thousands of antibodies are present in human plasma, though the amount of any one antibody is usually quite low under normal circumstances. The relative dimensions and molecular masses of some of the most important plasma proteins are shown in Figure 50-1. 

SIRTOR] C R, BOSISIO R, PAZZUCCONI F, BONDIOLI A, GATTI E, LOVATI M R and MURPHY P (2002) Soy Milk with a High Glycitein Content Does Not Reduce Low-Density Lipoprotein Cholesterolemia in Type II Hypercholesterolemic Patients. Nutr Metab. 46 (2) 88-92. 

There has been some evidence of a higher antioxidant effect when both flavonoids and a-tocopherol are present in systems like LDL, low-density lipoproteins (Jia et al., 1998 Zhu et al, 1999). LDL will incorporate a-tocopherol, while flavonoids will be present on the outside in the aqueous surroundings. A similar distribution is to be expected for oil-in-water emulsion type foods. In the aqueous environment, the rate of the inhibition reaction for the flavonoid is low due to hydrogen bonding and the flavonoid will not behave as a chain-breaking antioxidant. Likewise, in beer, none of the polyphenols present in barley showed any protective effect on radical processes involved in beer staling, which is an oxidative process (Andersen et al, 2000). The polyphenols have, however, been found to act synergistically... 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Dysfunction of the endothelium allows lipoproteins, predominantly low-density lipoprotein (LDL) cholesterol, and inflammatory cells, namely monocytes and T lymphocytes, to migrate from the plasma to the sub-endothelial space. Monocyte-derived macrophages ingest lipoproteins to form foam cells. Macrophages also secrete growth factors that promote smooth muscle cell migration from the media to the intima. A fatty streak consists of lipid-laden macrophages and smooth muscle cells and is the earliest type of atherosclerotic lesion. 

FIGURE 9-1. Lipoprotein structure. Lipoproteins are a diverse group of particles with varying size and density. They contain variable amounts of core cholesterol esters and triglycerides, and have varying numbers and types of surface apolipoproteins. The apolipoproteins function to direct the processing and removal of individual lipoprotein particles. (Reprinted from LipoScience, Inc. with permission.)... 

Metformin also has been shown to produce beneficial effects on serum lipid levels and thus has become a first-line agent for type 2 DM patients with metabolic syndrome. Triglyceride and low-density lipoprotein (LDL) cholesterol levels often are reduced by 8% to 15%, whereas high-density lipoprotein (HDL) cholesterol improves by approximately 2%. A modest weight loss of 2 to 3 kg (4.4—6.6 lb) also has been reported with metformin therapy. Metformin often is used in combination with a sulfonylurea or a thiazolidinedione for synergistic effects. 

In addition to effects on bone, raloxifene may have effects in breast tissue and on the cardiovascular system. A secondary end point of the MORE trial evaluated the effects of raloxifene on the primary prevention of breast cancer and found a significant reduction in all types of breast cancer.33 Raloxifene decreases total and low-density lipoprotein (LDL) cholesterol,34 and studies are evaluating its effect on reducing the risk of cardiovascular disease.35... 

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