Flip-flop movement, phospholipid

The physiological significance of this metabolic pathway in brain is unknown. Its occurrence in nervous tissue might be of some importance due to the possibility for the nerve cell to enrich its Ptd-choline fraction of polyunsaturated fatty acids, particularly 20 4 and 22 6, Moreover, the Ptd-choline synthesis by the methylation pathway in red blood cells has been indicated to represent a mechanism for an enzymeHnediated flip-flop of phospholipids from the cytoplasmic to the outer surface of erythrocyte m nbranes, producing fluidity variations in the same membrane vhich might affect ion movement and enzyme activities. It is possible that such implication can be drawn also for nervous membranes,... 

Phospholipids, which are one of the main structural components of the membrane, are present primarily as bilayers, as shown by molecular spectroscopy, electron microscopy and membrane transport studies (see Section 6.4.4). Phospholipid mobility in the membrane is limited. Rotational and vibrational motion is very rapid (the amplitude of the vibration of the alkyl chains increases with increasing distance from the polar head). Lateral diffusion is also fast (in the direction parallel to the membrane surface). In contrast, transport of the phospholipid from one side of the membrane to the other (flip-flop) is very slow. These properties are typical for the liquid-crystal type of membranes, characterized chiefly by ordering along a single coordinate. When decreasing the temperature (passing the transition or Kraft point, characteristic for various phospholipids), the liquid-crystalline bilayer is converted into the crystalline (gel) structure, where movement in the plane is impossible. 

Although phospholipids diffuse laterally in the plane of the bilayer and rotate more or less freely about an axis perpendicular to this plane, movements from one side of the bilayer to the other are a different matter. Diffusion across the membrane, a transverse, or flip-flop, motion, requires getting the polar head-group of the phospholipid through the... 

Lateral movement of phospholipid molecules is usually relatively rapid. Flip-flop, the transfer of a lipid molecule from one side of a lipid bilayer to the other, is rare. 

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... 

How the asymmetric distribution of phospholipids in membrane leaflets arises is still unclear. In pure bilayers, phospholipids do not spontaneously migrate, or flip-flop, from one leaflet to the other. Energetically, such flip-flopping is extremely unfavorable because it entails movement of the polar phospholipid head group through the hydrophobic interior of the membrane. To a first approximation, the asym-... 

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