Lipids transport

Symptoms of Essential Fatty Acid Deficiency in Humans Include Skin Lesions Impairment of Lipid Transport... 

THE LIVER PLAYS A CENTRAL ROLE IN LIPID TRANSPORT METABOLISM... 

Rye K-A et al Overview of plasma lipid transport. In Plasma Lipids and Their Role in Disease. Barter PJ, Rye K-A (editors). Harwood Academic Publishers, 1999. 

During, A., Dawson, H.D., and Harrison, E.H., Carotenoid transport is decreased and expression of the lipid transporters SR-Bl, NPCILI, and ABCAl is down-regulated in Caco-2 cells treated with ezetimibe, J. Nutr., 135, 2305, 2005. 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

It needs to be noted that apart from expression of lipoprotein receptors, RPE itself expresses several apolipoproteins (Bartl et al., 2001 Ishida et al., 2004 Li et al., 2006 Malek et al., 2003 Tserentsoodol et al., 2006a). So far, six apolipoproteins have been identified as being expressed by the RPE, namely, apolipoprotein A-I (ApoA-I), ApoB, ApoC-I, ApoC-II, ApoE, and ApoJ (clusterin) (Bailey et al., 2004 Bartl et al., 2001 Ishida et al., 2004 Li et al., 2006 Malek et al., 2003 Tserentsoodol et al., 2006a). In addition to their functions as lipid transporters and receptor ligands, apo-lipoproteins can act as modulators of several enzymes. The basic characteristics of apo-lipoproteins expressed by the RPE are described below. 

Apart from SR-BI, SR-BII, CD36, and ABCA1, a microarray analysis of gene expression in human RPE reveals some additional lipid transporters that might potentially be involved in intracellular transport of carotenoids and/or their efflux from the RPE cells into the neural retina or out of the retina into the choroidal blood (van Soest et al., 2007). These include other ABC... 

Kim, WS, Weickert, CS, and Gamer, B, 2008. Role of ATP-binding cassette transporters in brain lipid transport and neurological disease. JNeurochem 104, 1145-1166. 

Tserentsoodol, N, Gordiyenko, NV, Pascual, I, Lee, JW, Fliesler, SJ, and Rodriguez, IR, 2006a. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors. 

Chino, H. 1985. Lipid transport Biochemistry of hemolymph lipophorin. In Comprehensive Insect Physiology, Biochemistry, and Pharmacology, eds. Kerkut G. A. and Gilbert L. I., Oxford Pergamon Press, 10 115-134. 

Tsujishita, Y. and Hurley, J. H. 2000. Structure and lipid transport mechanism of a StAR-related domain. Nat. Struct. Biol., 7(5) 408 114. 

LBPs are likely to have conventional roles in the energy metabolism and transport of lipids in nematodes for membrane construction, etc. Many parasitic helminths have deficiencies in the synthesis of some lipids and so their lipid acquisition, transport and storage mechanisms clearly need to be specialized and therefore pertinent to the host-parasite relationship (Barrett, 1981). From a practical point of view, lipid transporter proteins may also be important in the delivery of anthelmintic drugs to their target most anthelmintics are hydrophobic and if they do not distribute to their site of action within the parasites by simple diffusion across and along membranes, then the parasite s own carrier proteins may be involved. 

The remaining major classes of water-soluble lipid transporter proteins (other than the polyproteins of nematodes see below) come from plants and helminths. Plants possess very small (approximately 9 kDa) helix-rich, fatty-acid-binding proteins, the structures of some of which are known (Lerche and Poulsen, 1998). A recently described class comes from cestodes these are also very small (approximately 8 kDa), presumably intracellular, and helix-rich, and bind anthelmintic drugs in addition to fatty acids (Janssen and Barrett, 1995 Barrett et al., 1997). The only helix-rich small (approximately 14 kDa) lipid transporter from vertebrates is the acetyl-CoA-binding protein (Kragelund et al., 1993). 

Nothing is yet known of the transmembrane lipid transporters of nematodes, so this chapter will concentrate on those proteins that appear to be unique to nematodes or those that are of a type familiar in other animal groups (principally vertebrates) but exhibit modifications of structure and function that are unusual to nematodes. 

There are many more ways to build a lipid transport protein for small lipids than previously known. The NPAs, for instance, have similar ligand-binding propensities to similarly sized LBPs of vertebrates, but are helix-rich rather than being P-rich. The LBP-20-type proteins represent yet another novel type of LBP. 

Borst, P., Zelcer, N., van Helvoort, A., ABC transporters in lipid transport, Biochim. Biophys. Acta 2000, 1486, 128-144. 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

Sleat, D. E., Wiseman, J. A., El-Banna, M. et al. Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc. Natl Acad. Sci. U.S.A. 101 5886-5891, 2004. 

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