Biology Reference
In-Depth Information
and are ATP-dependent transporters that move lipids to the outer leaflet (exofacial)
membrane surface. They have been associated with the ABC class of transporters. The third
family of lipid translocators is the scramblases, whose function is to move lipids bidirection-
ally across the membrane without use of ATP. Scramblases are inherently nonspecific and
function to randomize the distribution of newly synthesized phospholipids and may be
involved in membrane disruption events associated with cell death. In the case of the
well-studied erythrocyte, net flip-flop rates are: PS
>
PE
>
PC
>
SM.
Some General Conclusions from Flip-Flop Studies
Flip-flop of proteins and carbohydrates (in the form of glycoproteins and glycolipids) is
absolutely prohibited. Inherent rates of membrane phospholipid flip-flop are very slow,
with half-lives varying from days to weeks. This rate can be substantially enhanced (10
3
to
10
5
fold) by the simple inclusion of a trans-membrane protein. Cholesterol, diacylglycerol,
and free fatty acids have high inherent rates of flip-flop. Cell membranes have families of
lipid translocators known as flippases, floppases and scramblases whose functions are to
accurately maintain proper lipid asymmetry.
F. LIPID MELTING BEHAVIOR
The simple cartoon depiction of a lipid bilayer is deceptive. The lipid bilayer, existing in
what is more correctly termed the 'lamellar phase', is highly dynamic and can actually exist
in many related phases in addition to the lamellar state. Although the lamellar phase domi-
nates biological membrane structure, many and perhaps even most membrane polar lipids,
when isolated, would prefer to exist in exotic non-lamellar phases. It is the lipid mixtures that
stabilize the lamellar phase. A variety of non-lamellar phases are discussed in Chapter 10.
However, even the seemingly simple lamellar phase is complex and can exist in several vari-
ations. We will first discuss simple melting of the lamellar phase from the solid-like gel (L
b
'
for PCs) to the fluid-like liquid crystalline (L
) phase. Lipid bilayers should not be thought of
as existing as either a hard solid or water-like fluid but more like what would be observed
upon melting bacon grease. The gel state is a soft solid while the liquid crystalline state is
a viscous fluid.
A major theme of Chapter 4 was the effect of fatty acyl chain length and degree of unsa-
turation on 'melting' temperature (expressed as T
m
s). But why do fatty acyl chains melt at
all?
Figure 9.21
depicts the steps involved in melting of a saturated fatty acyl chain. A
section of an un-melted, trans state, saturated fatty acid is shown in
Figure 9.21
a. Newman
projections of a short segment of the chain are shown in
Figure 9.21
b. Upon heating the
chain, rotation occurs around all C
a
C bonds, for example the bond connecting carbons
2and3.Thetrans configuration (
Figure 9.21
b, left) has the lowest possible energy
(
Figure 9.21
c) as the largest groups, carbon 1 and carbon 4, are as far apart as possible.
Upon clockwise rotation, as the large C-4 passes a H, steric hindrance is encountered as
depicted in the eclipsed state (
Figure 9.21
b, middle). The eclipsed state is an unfavorable,
high-energy state (
Figure 9.21
c). Further rotation relieves some of the steric stress resulting
in another low energy state referred to as the gauche state (
Figure 9.21
b, right). The gauche
state is lower energy than the eclipsed state, but higher energy than the trans state, since
e
