Biology Reference
In-Depth Information
An obvious question is how such a simple molecule can affect so many seemingly unrelated
processes. To accomplish this, DHA must be exerting its influence at some fundamental level
that is common to many types of cells and tissues. Possible non-exclusive modes of action for
DHA include: (1) eicosanoid biosynthesis; (2) protein activity through direct interaction; (3)
protein activity through indirect interactions involving transcription factors; (4) lipid peroxi-
dation products; (5) membrane structure and function; and (6) lipid raft structure and function
[50,51]
. Previous chapters in this topic have discussed the enormous change in lipid physical
properties that affect membrane structure and function, occurring when a single double bond
is added to a saturated acyl chain.
Table 15.3
shows a list of these properties. Since double
bonds have such an enormous effect on membranes it seems logical to predict that the
DHA with 6-double bonds might be the most influential membrane fatty acid of all. Indeed,
many biophysical studies on lipid monolayer and bilayer properties have been reported
[50,52,53]
. The problem is that none of the listed properties are unique to DHA, but instead
are characteristic to some extent of all polyunsaturated fatty acids. In most, but not all, exam-
ples DHA does exert a larger effect than other less unsaturated fatty acids, but this difference
is probably not sufficient to account for DHA's unusual health benefits. One possibility for
DHA's molecular mode of action is in affecting important cell signaling processes by altering
the composition, size, structure, and stability of lipid rafts. Initial investigations have demon-
strated that DHA does indeed affect lipid raft structure and cell signaling
[54
56]
.
It is likely that no single membrane property is sufficient to account for DHA's health
benefits, but rather a combination of as yet unidentified DHA-affected properties is required.
But what exactly are these properties? The answer to this conundrum will require further
research into the molecular aspects of membrane structure and function. It can be predicted
that in the near future the next major advance in membranes will involve understanding
exactly what a lipid raft is at the molecular level. How many types of lipid rafts and lipid
non-rafts are there and how do they control cellular events? Once the very fundamental
questions about membrane structure are better understood, it should be possible to design
new paradigms to benefit the human condition.
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SUMMARY
The complexity of membrane structure and function outlined in this topic suggests
a wealth of potential targets to alleviate human afflictions. This chapter investigates how
liposomes can be modified for targeted drug delivery. The liposomes must be non-leaky
and able to avoid the reticulo-endothelial system (RES). Several types of drug-carrying
liposomes are discussed including 'Stealth' liposomes (coated with polyethyleneglycol),
Thermo-liposomes (made from lipid mixtures with a phase transition temperature ~2
4
C
above physiological), pH-sensitive liposomes (containing a titratable group, often derivatives
of homocysteine or succinate) and several targeted liposomes (with specific antibodies,
lectins, receptors, and vitamins attached to the liposome surface). Also discussed are the
effects of dietary fatty acids on membrane structure and function as it influences human
health. In this regard, harmful trans fatty acids (TFAs) are contrasted with the beneficial
omega-3 fatty acid, docosahexaenoic acid (DHA).
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