Phospholipids translocation

While examples such as these provide evidence that strong interactions of negatively-charged membrane lipids with membrane proteins the role in maintaining asymmetric distributions of lipids aaoss biological membranes is unclear. In any event such effects are likely to be of minor importance relative to actively mediated phospholipid translocation processes. 

Gurtovenko, A.A., Onike, O.I., Anwar, J. Chemically induced phospholipid translocation across biological membranes. Langmuir 2008, 24, 9656-60. 

The control of the processes of phospholipid translocation and scrambling by cytoplasmic calcium concentration is known to be one factor in regulating the appearance of phosphatidylserine on the cell surface. There is now evidence that other factors are involved in modulating membrane phospholipid distribution and for preserving phospholipid homeostasis. Current research is directed to clarify the role of these agents and to establish any connections with the initiation of apoptosis. 

Explain why spontaneous phospholipid translocation (the movement of a molecule from one side of a bilayer to the other) is so slow. 

Because membranes are dynamic structures, the mechanism by which they are synthesized is complex. Currently, little is known about the synthesis of the membrane bilayer except for the following features phospholipid translocation across membranes and the intracellular transfer of phospholipids between membranes. 

If recently synthesized phospholipid molecules remained only on the cytoplasmic surface of the ER, a monolayer would form. Unassisted bilayer transfer of phospholipid, however, is extremely slow. (For example, half-lives of 8 days have been measured across artificial membrane.) A process known as phospholipid translocation is now believed to be responsible for maintaining the bilayer in membranes (Figure 12F). Transmembrane movement of phospholipid molecules (or flip-flop), which may occur in as little as 15 seconds, appears to be mediated by phospholipid translocator proteins. One protein (sometimes referred to as flippase) that transfers choline-containing phospholipids across the ER membrane has been identified. Because the hydrophilic polar head group of a phospholipid molecule is probably responsible for the low rate of spontaneous translocation, an interaction between flippase and polar head groups is believed to be involved in phosphatidylcholine transfer. Translocation results in a higher concentration of phosphatidylcholine on the lumenal side of the ER membrane than that... 

Phospholipid translocator proteins, phospholipid exchange proteins, and transition vesicles are involved in the complicated process of membrane synthesis and delivery of membrane components to their cellular destinations. 

Membrane phospholipids are synthesized on the cytoplasmic side of SER membrane. Because the polar head groups of phospholipid molecules make transport across the hydrophobic core of a membrane an unlikely event, a translocation mechanism is used to transfer phospholipids across the membrane to ensure balanced growth. Choline-containing phospholipids are found in high concentration on the lumenal side of ER membrane because a prominent phospholipid translocator protein called flippase preferentially transfers this class of molecule. 

Fig. 1 - Phospholipid translocation rate in vesicles with different phosphatidylcholine chain length.

Fig. 3 - A. Light scattering increase induced by the temperature in DPPC vesicles. B. DPPC vesicles light scattering increase and phospholipid translocation rate o—o at various myristic acid concentrations.

T. Yoshikado, T. Takada, T. Yamamoto, H. Yamaji, K. Ito, T. Santa, H. Yokota, Y. Yatomi, H. Yoshida, J. Goto, S. Tsuji and H. Suzuki, Itraconazole-induced cholestasis involvement of the inhibition of bile canicular phospholipid translocator MDR3/ABCB4, Mol Pharmacol, 2011, 79, 241-250. 

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