Phospholipids transport

Klucken, J., et al. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. U. S. 

Mammalian genetic diseases of cellular sterol and phospholipid transport... 

In some of the earliest studies of phospholipid transport between the inner and the outer membranes of E. coli, radiolabeling of PE revealed that the specific radioactivity of this lipid was 5-fold higher in the inner membrane than the outer membrane, immediately following a 30-s pulse with [ HJglycerol (A.M. Donohue-Rolfe, 1980). During the chase period, the specific radioactivity of the outer membrane increased, while that of the inner membrane decreased. After several minutes, the specific activities of both membranes asymptotically approached the same value, which indicated radioequilibration between the membranes. The ty2 for the translocation of PE was determined to be 2.8 min. The transport in these studies was independent of protein synthesis, lipid synthesis, and ATP synthesis. It appeared, however, to be dependent upon the cell s proton motive force. Analysis of LPS... 

Voelker, D.R. 2005. Bridging gaps in phospholipid transport. Trends Biochem. Sci. 30 396-404. 

The surface pressure of the phospholipid monolayer on the trough is critical and depends on the phospholipid. Transport from the trough to the ellipsometer cuvette was done in a special sample holder such that exposure of the bilayer to air was prevented. 

In the present paper we describe the results of our studies on the biosynthesis and turnover of phosphatidyl choline (PC) in rat brain. We will discuss the apparent lack of phospholipid transport mechanisms in cell membranes of the CNS and will show that all brain subcellular fractions seem to have a certain degree of independence for the synthesis of this phospholipid. The presence of rapid and slow turnover pools for PC will be described and possible explanations for these findings will be presented. 

Fatty acids in which hydrogen is substituted by other elements have also been employed. lodination of an unsaturated fatty acid yields an iodine-tagged molecule which has been used to study fat deposition and phospholipide transport. - Such a tagged molecule is, however, unphysi-... 

Phospholipids. Phospholipids, components of every cell membrane, are active determinants of membrane permeabiUty. They are sources of energy, components of certain enzyme systems, and involved in Hpid transport in plasma. Because of their polar nature, phosphoUpids can act as emulsifying agents (42). The stmcture of most phosphoUpids resembles that of triglycerides except that one fatty acid radical has been replaced by a radical derived from phosphoric acid and a nitrogen base, eg, choline or serine. 

Proteins that can flip phospholipids from one side of a bilayer to the other have also been identified in several tissues (Figure 9.11). Called flippases, these proteins reduce the half-time for phospholipid movement across a membrane from 10 days or more to a few minutes or less. Some of these systems may operate passively, with no required input of energy, but passive transport alone cannot establish or maintain asymmetric transverse lipid distributions. However, rapid phospholipid movement from one monolayer to the other occurs in an ATP-dependent manner in erythrocytes. Energy-dependent lipid flippase activity may be responsible for the creation and maintenance of transverse lipid asymmetries. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

Family of enzymes phosphorylating phosphatidylinositol (Ptdlns), PtdIns(4)phosphate, and PtdIns(4,5)phosphate in the 3-position. The Ptdlns(3 phospholipids are second messengers in processes like cell growth, cytoskeletal rearrangement, and vesicular transport. PI 3-kinases are heterodimers composed of a catalytic and a regulatory subunit. The enzymes are activated by insulin, many growth factors, and by a variety of cytokines. Their activity can be inhibited by wortmannin and LY294002. 

Fat absorbed from the diet and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, the problem of how to transport them in the aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesteryl esters) with amphipathic hpids (phospholipids and cholesterol) and proteins to make water-miscible hpoproteins. 

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Figure 26-5. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be initiated by pre 3 HDL binding to the ABC-1 transporter protein via apo A-l. Cholesterol is then moved out of the cell via the transporter, lipidating the HDL, and the larger particles then dissociate from the ABC-1 molecule. (C, cholesterol CE, cholesteryl ester PL, phospholipid ACAT, acyl-CoA cholesterol acyltransferase LCAT, lecithinicholesterol acyltransferase A-l, apolipoprotein A-l LDL, low-density lipoprotein VLDL, very low density lipoprotein.) LDL and HDL are not shown to scale.

In addition to phospholipids, cell membranes contain protein molecules that carry out special functions such as transporting ions and molecules through the membrane. 

All enveloped human vimses acquire their phospholipid coating by budding through cellular membranes. The maturation and release of enveloped influenza particles is illustrated in Fig. 3.8. The capsid protein subunits are transported flom the ribosomes to the nucleus, where they combine with new viral RNA molecules and are assembled into the helical capsids. The haemagglutinin and neuraminidase proteins that project fiom the envelope of the normal particles migrate to the cytoplasmic membrane where they displace the normal cell membrane proteins. The assembled nucleocapsids finally pass out from the nucleus, and as they impinge on the altered cytoplasmic membrane they cause it to bulge and bud off completed enveloped particles flxm the cell. Vims particles are released in this way over a period of hours before the cell eventually dies. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

In this in vitro system, the presence of serum in cell culture medium is not necessary, but the type of transwell is important (the total amount of H-triglycerides secreted was two-fold higher when using 3 pm versus 1 pm pore size transwells), and oleic acid supplementation is required for the formation and secretion of CMs as well as the transport of 3-carotene through Caco-2 cells. Finally, the presence of Tween 40 does not affect CM synthesis and secretion in this in vitro cell culture system. Thus, CMs secreted by Caco-2 cells were characterized as particles rich in newly synthesized H-triglycerides (90% of total secreted) containing apolipoprotein B (30% of total secreted) and H-phospholipids (20% of total secreted) and with an average diameter of 60 nm. These characteristics are close to those of CMs secreted in vivo by enterocytes. ... 

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