Biology Reference
In-Depth Information
TABLE 9.1
Flip-Flop Rates (Expressed as Half-Lives) for NBD-PE as
Followed by Quenching of NBD Fluorescence with Dithionite.
Large Unilamellar Vesicles (LUVs) were Made from the Listed
PCs with 1 % NBD PE Incorporated (25
C).
PC
Flip-Flop Half Life
(
t
1/2
(h))
16:0,16:0
>
70
18:0,18:1
11.5
1.6
18:1,18:1
8.1
0.6
18:0,18:2
4.9
0.9
18:2,18:2
1.9
0.4
18:3,18:3
1.3
0.3
18:0,22:6
0.29
0.02
22:6,22:6
0.087
0.006
quenching of NBD fluorescence with dithionite. As the number of double bonds comprising
the bilayer increases, so does the flip-flop rate (
Table 9.1
). For example, flip-flop of NBD-PE in
22:6,22:6 PC with 12 double bonds is at least 10
3
times greater than in 16:0,16:0 PC with no
double bonds. Flip-flop is related to the acyl chain double bond content in the lipid bilayer
interior.
Flippase, Floppase, and Scramblase
From the very first determinations of lipid asymmetry in erythrocytes, it was evident that
lipid asymmetry was complex. Particularly troublesome was the observation that the distri-
bution of PS, unlike the other phospholipids, was almost totally asymmetric. Bretscher real-
ized the importance of PS being found exclusively on the inner membrane leaflet. In 1972
[10]
he proposed the existence of an energy-dependent membrane protein whose function was to
flip PS from the outer membrane leaflet to the inner leaflet, thus preserving the total
asymmetric distribution of PS. He even coined the term 'flippase' for this protein. An
ATP-dependent flippase was later discovered by Seigneuret and Devaux in 1984
[12]
. This
protein proved to be only one of a family of related membrane proteins called 'flippases',
'floppases', and 'scramblases' whose functions are to correctly distribute the various phos-
pholipids across membranes
[15,16]
.
Newly synthesized phospholipids are initially incorporated into the inner membrane
leaflet after which they are subsequently distributed by a variety of lipid translocators
[15,16]
. Although the term 'flippase' initially referred in general to any lipid translocator, it
now refers to proteins that move lipids to the inner leaflet (cytofacial) membrane surface.
They are ATP-dependent transporters. The flippase is highly selective for PS and functions
to keep this lipid from appearing on the outer surface of the cell. Upon aging, PS starts to
accumulate on the cell exterior, triggering apoptosis. Floppases are the opposite of flippases
