Lipids transport between membranes

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]. 

Transport of membrane lipids from the site of synthesis to the target membranes has been postulated to be mediated by membrane vesicles, by lipid transport proteins and/or to occur at contact sites between membranes [1-3]. Vesicular-mediated lipid transport between plant membranes has been reconstituted in cell-free systems. The results suggest that transport of lipids from endoplasmic reticulum (ER) to the Golgi apparatus [4,5] or to the chloroplast envelope (Sandelius and Rantfors, unpublished) and from the envelope to the thylakoid [6] is metabolically regulated, as shown by temperature dependence and requirement of and/or stimulation by ATP and cytosol or stroma. 

Transport of proteins and lipids occurs between the organelles of the secretory pathway, i.e. endoplasmic reticulum (ER), Golgi, endosomes, lysosomes and the plasma membrane. 

In many eukaryotic plasma membranes, PS resides in the inner leaflet (Schroit and Zwaal, 1991 Zachowski, 1993). This transbilayer distribution of membrane hpids is not a static situation but a result of balance between the inward and outward translocation of phospholipids across the membranes. Recent studies showed that the transbilayer lipid asymmetry is regulated by several lipid transporter proteins, such as aminophospholipid translocase (Daleke and Lyles, 2000), ATP-binding cassette transporter family (van Helvoort et al, 1996 Klein et al, 1999), and phospholipid scramblase (Zhou et al, 1997 Zhao et al, 1998). An increment of intracellular due to cell activation, cell injury, and apoptosis affects the activities of these transporters, resulting in exposure of PS (Koopman et al, 1994 Verhoven et al, 1995) and PE (Emoto et al, 1997) on the cell surface. 

Experimental Results and Comparisons with the Classical Lipid Barrier Model. Some typical experimental data are presented in Figure 1 for the transport of g-estradiol. In each of the experiments a lag-time of 1.5 to 2.5 hours were followed by linear steady state fluxes. The effective permeability coefficient, Peff> was calculated from such data using Equation 1 under sink conditions (i.e., Cj/K Cr/Kr where, Kj is the partition coefficient between membrane and donor phase and Kr the partition coefficient between membrane and receiver phase.)... 

Biophysical processes involving membrane transport are also influenced by hydration. The size of the hydration shell surrounding small ions and the presence of water in the cavities of ionic channels or in the defects between membrane lipids strongly affect the rates at which the ions cross a cell membrane. 

Partition coefficients are of extreme value in medicinal chemistry as they may be related to drug transfer across membranes and binding at active centres. The parameter logP models various kinds of transport between aqueous and lipid phases and P is defined as the partition coefficient of a substance between water and n-octanol. The free energy of the transport process is often linearly related to standard hydro-phobic parameters (re) for substituents (X) determined from Px values for substituted phenoxyacetic acids and that for the parent acid Ph (Equation 16). 

The enterocytes of the small intestine can be isolated and used for study of intracellular aspects of intestinal lipid transport like triglyceride synthesis [52]. The disappearance of the mucus barrier during isolation of the epithelial cells results in plasma membrane disintegration and loss of cellular integrity when the cells are exposed to bile salts. As is the case for brush border vesicles, the system of isolated cells does not allow study of interaction between enterocytes and lipids dispersed in a form that resembles physiological conditions, i.e. solubilized in mixed bile salt micelles. 

A FIGURE 18-8 Proposed mechanisms of Golgi-independent transport of cholesteroi and phospholipids between membranes. In mechanism (a), vesicles transfer lipids between membranes without passing through the Golgi apparatus. In mechanism (b), lipid transfer is a consequence of direct contact between membranes that is mediated by... 

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