Low-density lipoproteins uptake

Grove RI, Mazzucco C, Allegretto N, et al. Macrophage-derived factors increase low-density lipoprotein uptake and receptor number in cultured human liver cells. J Lipid Res 1991 32 1889-1897. 

Zwaka TP, Hombach V, et al. C-reactive protein-mediated low density lipoprotein uptake by macrophages implications for atherosclerosis. Circulation 2001 103 1194-7. 

Zwaka, T.P., Hombach, V., and Torzewski, J. (2001) C-Reactive Protein-Mediated Low-Density Lipoprotein Uptake by Macrophages—Implications for Atherosclerosis, Circulation 103,1194-1197. 

Kuda, O., Pietka, T.A., Demianova, Z., Kudova, E., Cvacka, J., Kopecky, J. Abumrad, N.A. Sulfo-A -succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164 SSO also inhibits oxidized low density lipoprotein uptake by macrophages. J. Biol. Chem. 2013, 288 15547-15555. 

Aviram M, Bias K. Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. Ann Nutr Metah 1993 37 75-84. 

Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6 1380-1387... 

HoflT, H.F., O NeU, J., Chisolm, G.M., Cole, T.B., Quehen-berger, O., Esterbauer, H. and Juetgens, G. (1989). Modification of low-density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis 9, 538-549. 

Tserentsoodol, N, Sztein, J, Campos, M, Gordiyenko, NV, Fariss, RN, Lee, JW, Fhesler, SJ, and Rodriguez, IR, 2006b. Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-... 

Urpi-Sarda M, Jauregui O, Lamuela-Raventos RM, Jaeger W, Miksits M, Covas MI and Andres-Lacueva C. 2005. Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal Chem 77(10) 3149—3155. 

The answer is a. (Katzung, p 590.) Bile acids are absorbed primarily in the ileum of the small intestine. Cholestyramine binds bile acids, preventing their reabsorption in the jejunum and ileum. Up to 10-fold greater excretion of bile acids occurs with the use of resins. The increased clearance leads to increased cholesterol turnover of bile acids. Low-density lipoprotein receptor upregulation results in increased uptake of LDL. This does not occur in homozygous familial hypercholesterolemia because of lack of functioning receptors. 

The bulk of pinocytosis in the nervous system is mediated by clathrin-mediated endocytosis (CME) [55] and this is the best-characterized pathway. More detail about clathrin-mediated pathways will be given when receptor-mediated endocytosis and the synaptic vesicle cycle pathways are considered. Pinocytosis through CME is responsible for uptake of essential nutrients such as cholesterol bound to low density lipoprotein (LDL) and transferring, but also plays a role in regulating the levels of membrane pumps and channels in neurons. Finally, CME is critical for normal synaptic vesicle recycling. 

Metformin is the only biguanide available in the United States. It enhances insulin sensitivity of both hepatic and peripheral (muscle) tissues. This allows for increased uptake of glucose into these insulin-sensitive tissues. Metformin consistently reduces A1C levels by 1.5% to 2%, FPG levels by 60 to 80 mg/dL, and retains the ability to reduce FPG levels when they are very high (>300 mg/dL). It reduces plasma triglycerides and low-density lipoprotein (LDL) cholesterol by 8% to 15% and modestly increases high-density lipoprotein (HDL) cholesterol (2%). It does not induce hypoglycemia when used alone. 

Koller-Lucae SM, Schott H, Schwendener RA. Low density lipoprotein and liposome mediated uptake and cytotoxic effect of N -octadecyl-l-P-o-arabino-furanosylcytosine (NOAC) in Daudi lymphoma cells. Br J Cancer 1999 80 1542. 

A central event in the generation of plaque is the uptake of low density lipoproteins (LDL) by macrophages in the subendothelial space. LDL enters this space through the damaged endothelial cells. The uptake occurs via endocy-tosis, after the binding of LDL to one of three receptors on the macrophage ... 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

Pretreatment of neurons by flavonoids (epicatechin and its 3 -D-methylether, kaempferol) strongly inhibits cell death induced by oxidized low-density lipoproteins (ox-LDL) without reduction of ox-LDL uptake or intracellular oxidative stress. Cell protection is selectively correlated to inactivation of JNK, thus suggesting that, irrespective of their H-atom donating activity, flavonoids can selectively attenuate a pro-apoptotic signaling cascade involving MAPKs. 

An increased rate of metabolic clearance has been observed after removal of sialic acid from human, low-density lipoprotein in vivo.472 Sialic acid controls the receptor-mediated uptake of this lipoprotein by fibroblasts. Removal of sialic acid residues accelerates the rate of internalization of the lipoprotein and, subsequently, the regulation of the metabolism of cellular cholesterol.473... 

Uptake of low-density lipoprotein has been studied479 as a prototype of a receptor-mediated pathway for internalization of external macromolecules. It is a coupled process by which selected, extracellular proteins or peptides are first bound to specific, cell-surface receptors, and then rapidly internalized by the cell. Internalization follows clustering of receptors in specialized regions of the cell surface, called coated pits, that invaginate, to form coated vesicles. 

Mammalian cells acquire cholesterol either by de novo synthesis from acetyl-coen-zyme A (CoA) or via the low-density lipoprotein (LDL)-receptor-mediated uptake of LDL particles that contain cholesterol esterified with long-chain fatty acids. These LDL cholesterol esters are subsequently hydrolyzed in lysosomes, after which free cholesterol molecules become available for synthesis of membranes, steroid hormones, bile acids, or oxysterols [1]. 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

Figure 3.10 Uptake of blood constituents by the mammary gland CoA, coenzyme A G-3-P, glycerol-3-phosphate FFA, free fatty acid FA, fatty acid TG, triglyceride, VLDL, very low density lipoprotein (from Hawke and Taylor, 1995).

When the diet contains more fatty acids than are needed immediately as fuel, they are converted to triacylglycerols in the liver and packaged with specific apolipoproteins into very-low-density lipoprotein (VLDL). Excess carbohydrate in the diet can also be converted to triacylglycerols in the liver and exported as VLDLs (Fig. 21-40a). In addition to triacylglycerols, VLDLs contain some cholesterol and cholesteryl esters, as well as apoB-100, apoC-I, apoC-II, apoC-III, and apo-E (Table 21-3). These lipoproteins are transported in the blood from the liver to muscle and adipose tissue, where activation of lipoprotein lipase by apoC-II causes the release of free fatty acids from the VLDL triacylglycerols. Adipocytes take up these fatty acids, reconvert them to triacylglycerols, and store the products in intracellular lipid droplets myocytes, in contrast, primarily oxidize the fatty acids to supply energy. Most VLDL remnants are removed from the circulation by hepatocytes. The uptake, like that for chylomicrons, is... 

The loss of triacylglycerol converts some VLDL to VLDL remnants (also called intermediate density lipoprotein, IDL) further removal of triacylglycerol from VLDL produces low-density lipoprotein (LDL) (Table 21-2). Very rich in cholesterol and cholesteryl esters and containing apoB-100 as their major apoli-poprotein, LDLs carry cholesterol to extrahepatic tissues that have specific plasma membrane receptors that recognize apoB-100. These receptors mediate the uptake of cholesterol and cholesteryl esters in a process described below. 

Electron micrograph of LDL particles (made electron-dense with covalently bound ferritin) bound to coated regions of a human skin fibroblast (97,000 X ). (From R. G. W. Anderson, M. S. Brown, and J. L. Goldstein, Role of the coated and endocytic vesicle in the uptake of receptor-bound low-density lipoprotein in human fibroblasts. Cell 10 351, 1977. Cell Press.)... 

Goldstein, J.L., R.G. Anderson, and M.S. Brown. 1982. Receptor-mediated endocytosis and the cellular uptake of low density lipoprotein. Ciba Found Symp 11. 

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