Transmembrane phospholipid translocation

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... 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

Bishop, W.R. Bell, R.M. (1988) Assembly of phospholipids into cellular membranes biosynthesis, transmembrane movement and intracellular translocation. Ararat. Rev. Cell Biol. 4, 579-610. Advanced review of the enzymology and cell biology of phospholipid synthesis and targeting. 

Magzoub, M., A. Pramanik, and A. Graslund (2005) Modeling the endosomal escape of cell-penetrating peptides transmembrane pH gradient driven translocation across phospholipid bilayers. Biochemistry 44,14890-14897. 

The lipids in a lipid bilayer may translocate across the bilayer from one monolayer to the apposed monolayer. This transmembrane translocation process, which is also known as flip-flop, is slow for lipids with large polar head groups such as glyc-erolipids and sphingophospholipids but can be fast in the case of lipids with very small polar moieties such as cholesterol. Typical first-order rate constants for transmembrane translocation of a phospholipid-like molecule in liquid-disordered phase bilayers prepared from l-palmitoyl-2-oleoylphosphatidylcholine (POPC) are s and may be about 10-fold slower in... 

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