Phospholipids transfer protein

Wirtz, K. W. A., 1991. Phospholipid transfer proteins. Annual Review of Biochemistry 60 73—99. 

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

ALNXGQVDTXLAPXV Probable phospholipid transfer protein -oat (fragment) alpha-amylase inhibitor, Oat-B N-terminal /l-27/4ve a sotiva[73% 0.3... 

The phosphatidylcholine in bile is synthesised in the endoplasmic reticulum of the hepatocyte and must be transported to the canalicular membrane. One possibility involves the nonspecific phosphatidylcholine transfer protein but a mouse null for this protein did not show reduced phosphatidylcholine secretion into bile and there was no compensatory increase in other phospholipids transfer proteins. However, the plasma membrane would receive a ready supply of phospholipid by insertion of vesicles, and the MDR3 protein translocates this molecule from the inner leafiet to the outer surface where there is contact with bile acids, as suggested by Smit and colleagues. The role of this transporter is shown in Figure 2.2. 

Pheromone (sex attractant). Ether extract of the stem, produced equivocal effect on Aspiculuris tetraptera, female and male Dacus dorsalis, male Mediterranean fruit flies, and male and female melon flies " k Pheromone (signaling). Ether extract of the stem, produced equivocal effect on Aspiculuris tetraptera, female and male Dacus dorsalis, male Mediterranean fruit flies, and male and female melon flies " k Phospholipidemic effect. Oil, administered to phospholipids transfer protein knockout (PLTPO)-deficient mice, produced an increase of phospholipids and free cholesterol in the VLDL-LDL region of PLTPO mice. Accumulation of phospholipids and free cholesterol was dramatically increased in PLTPO/HLO mice compared to PLTPO mice. Turnover studies indicated that coconut oil was associated with delayed catabolism of phospholipids and phospho-lipids/free cholesterol-rich particles. Incubation of these particles with hepatocytes of coconut-fed mice produced a reduced removal of phospholipids and free cholesterol by SRBI, even though SRBI protein expression levels were unchanged . 

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...

This volume has excellent reviews of biosynthetic pathways to glycerophospholipids and sphingolipids, phospholipid transfer proteins, and bilayer assembly. 

Many larger lipid carrier proteins are known. The 476-residue plasma cholesteryl ester transfer protein is discussed briefly in Chapter 22. Plasma phospholipid transfer proteins are of similar size.t/U A 456-residue human phospholipid-binding protein interacts with the lipopolysaccharide of the surfaces of gram-negative bacteria (Fig. 8-30) and participates in the immune response to the bacteria. It has an elongated boomerang shape with two cavities, both of which bind a molecule of phosphatidylcholine. Other plasma lipid transfer proteins may have similar structures/... 

How does the cell sort and transport phospholipids from the site of synthesis to other membranes in the cell One view is that phospholipid vesicles that bud from the endoplasmic reticulum are targeted to another membrane where the vesicles fuse with the membrane. Alternatively, phospholipid transfer proteins may be involved. Proteins that transfer phospholipids between membranes in vitro have been known for over 25 years but it has not been demonstrated that they function in this way in vivo. 

C22. Crain, R. C., and Zilversmit, D. B., Net transfer of phospholipid by the non-specific phospholipid transfer proteins from bovine liver. Biochim. Biophys. Acta 620, 37-48 (1980). 

P23. Poorthuis, B. J. H. M., and Wirtz, K. W. A., Increased cholesterol esterification in rat liver microsomes by purified non-specific phospholipid transfer protein. Biochim. Biophys. Acta 710, 99-105 (1982). 

T2. Tall, A. R, Abreu, E., and Shuman, J., Separation of a plasma phospholipid transfer protein from cholesterol ester/phospholipid exchange protein. J. Biol. Chem. 258, 2174-2180 (1983). 

Cleves, A., McGee, T., and Bankaitis, V, 1991a, Phospholipid transfer proteins A biological debut. Trends Cell. Biol. 1 30-34. 

Cleves, A.E., McGee, T Whitters, E. A., Champion, K.M., Aitken, J.R., Dowhan, W., Goebl, M., and Bankaitis, VA., 1991b, Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cell 64 789-800. 

Schneider M, Verges B, Klein A, Miller ER, Decker V, Desrumaux C, Masson D, Gambert P, Brun JM, Fruchart-Najib J, Blache D, Witztum JL, Lagrost L. Alterations in plasma vitamin E distribution in type 2 diabetic patients with elevated plasma phospholipid transfer protein activity. Diabetes 2004 53(10) 2633-9. 

Yazdanyar A, Yeang C, Jiang XC (2011) Role of phospholipid transfer protein in high-density lipoprotein-mediated reverse cholesterol transport. Curr Atheroscler Rep 13 242-248... 

Faire U, Leander K, Gigante B, Kavousi M, Hofinan A, Uitterlinden AG, van Duijn CM, Witteman JC, Jnkema JW, Schadt EE, van der Schoot E, Kastelein JJ, Khaw KT, Dullaart BE, van Tol A, Trip MD, Dallinga-Thie GM (2010) Genetic variation at the phospholipid transfer protein locus affects its activity and high-density lipoprotein size and is a novel marker of cardiovascular disease susceptibility. Circulation 122 470—477... 

Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR (2001) Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7 847-852... 

Krauss RM (2010) Phospholipid transfer protein and atherosclerosis genetic studies take aim at a moving target. Circulation 122 452 54... 

After synthesis in the various compartments of endoplasmic reticulum of alveolar type II cells, surfactant components are assembled in the cytosol into lamellar bodies. In the process of formation of lamellar bodies, the transfer of phospholipids between membranes is facilitated by phospholipid transfer proteins, which are nonenzymatic proteins found in all eukaryotic cells and which play an important role in lipid metabolism. There are three well-characterized phospholipid transfer proteins ... 

K. W. A. Wirtz Phospholipid transfer proteins revisited. Biochemical Journal 324, 353 0991). 

Beef brain, heart, and liver have been the most frequently used sources of purified phospholipid transfer proteins. From these tissues, three classes of transfer proteins have been identified a phosphatidylcholine-specific transfer protein, a phosphatidylinositol-specific transfer protein, and a nonspecific transfer protein. In addition to the purified proteins shown in Table I, other transfer proteins have been partially purified from a wide variety of tissues and organisms including rat intestine (Lutton and Zilversmit, 1976a), rat lung (Van Golde et al., 1980), sheep lung (Robinson et al., 1978), beef spleen (Metz and Radin, 1982), potato tubers (Kader, 1975), endosperm of germinating castor bean (Douady et al., 1980), Rhodopseudomonas sphaeroides (Cohen et al., 1979), and yeast (Cobon et al., 1976). 

Lipid transfer proteins have proved to be a useful tool for studying artificial and natural membranes (for a recent review see Bloj and Zilver-smit, 1981a). With the ability of phospholipid transfer proteins to replace selectively the phospholipid molecules on the exposed surfaces of membranes, information about the asymmetric distribution of phospholipids across a bilayer and the rate of transbilayer movement of phospholipid... 

Urizar, N. L., Dowhan, D. H., and Moore, D. D. (2000) The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. J. Biol. Chem. 275, 39313-39317. 

In 1968, Wirtz identified a soluble intracellular protein derived from rat liver that was capable of binding PC and transferring it from one population of (donor) membranes to a second population of (acceptor) membranes (K. Wirtz, 1968). Since this initial observation, many of these proteins have been identified in virtually all mammalian tissues, in plants, and in yeast and other microorganisms [5]. The well-characterized phospholipid transfer proteins fall into three main categories (i) those specific for PC (ii) those with... 

The transbilayer movement of phospholipids in microsomal membranes has been measured using several different approaches. Phospholipid transfer proteins were used to probe the transbilayer movement of lipids in preparations of liver microsomes that were first radiolabeled with lipid precursors in vivo (D.B. Zilversmit, 1977). The results from these experiments provided evidence that PC, PE, PS, and PI from both membrane leaflets were exchanged between labeled microsomes and excess acceptor membranes with a maximal t 2 of 45 min. 

Wirtz, K.W. 2006. Phospholipid transfer proteins in perspective. FEBS Lett. 580 5436-5441. 

Though chylomicrons and VLDLs are both substrates for LPL, the processing of the end-products of their metabolism is quite different. Chylomicron remnants recirculate until about 80% of their original TG content has been removed. These remnants retain almost the whole of their content of CE and retinyl ester. Excess surface molecules (mainly apo C proteins, cholesterol, and phospholipids) are transferred from the remnants, either spontaneously or by the activity of phospholipid transfer protein, mainly to HDLs. The chylomicron remnants, with apo E as the major ligand, are cleared quantitatively by hepatic receptors of the LDL receptor family. 

Phospholipid transfer protein is a plasma protein that promotes the transfer of phospholipids down a phospholipid concentration gradient, probably by a shuttle mechanism... 

Because of a rapid equilibrium between HDL core and surface lipids, CETP, phospholipid transfer protein, HL, EL, and scavenger receptor-BI each has the potential to modify the HDL surface lipid composition, and indirectly alter the affinity of apo A1 for HDL (Fig. 8). There is presently insufficient evidence to assess the relative significance of these factors in promoting apo A1 recycling or RCT either in human plasma or in mice. The most direct link between recycling and pre-beta,-HDL is that now linked to apo M in mice. 

Fig. 8. A model suggesting roles for scavenger receptor-BI (SR-BI), CETP, PLTP, HL, and apo M in the recycling of pre-beta,-HDL from large HDLs. Probable roles for these factors are supported by data but their quantitative contributions have not been determined. PLTP, phospholipid transfer protein FFA, fatty acid. Other abbreviations are defined in the list of abbreviations.

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