Biology Reference
In-Depth Information
polar head
rigid sterol rings
floppy tail
FIGURE 5.23
Cartoon depiction of the three sections of a sterol.
Overall, the molecule is quite flat. The molecular mode of action of the best understood sterol,
cholesterol
[31
e
33]
, will be discussed in detail in Chapters 9 and 10.
Interest in cholesterol is primarily due to its strong link to high blood pressure and heart
disease in man. But most aspects of cholesterol are not evil. Cholesterol was first isolated
from gallstones around 1758 by de La Salle. In 1815 Chevreul isolated cholesterol from
the unsaponifiable fraction of animal fat and coined the term cholesterine (from the Greek
word khole for bile). The major location of cholesterol in vertebrates is the brain, which
accounts for one quarter of the body's total cholesterol. In the plasma membrane of animal
cells cholesterol is usually the major polar lipid, often comprising more than 50% of the total
membrane lipids. It has even been reported that the ocular lens membrane is about 80 mol%
cholesterol! Cholesterol is therefore a major structural component of at least the plasma
membrane where it is involved in providing mechanical strength, controlling phase
behavior and supporting membrane lateral organization and stability. Cholesterol has
been proposed to be the molecular 'glue' that holds essential cell signaling lipid rafts
together (Chapter 8). In addition cholesterol is a precursor for all steroid hormones
(including progesterone, testosterone and estradiol), bile salts and vitamin D. Therefore,
cholesterol has two distinct roles: as a structural component of membranes and as
a precursor for other essential biochemicals.
In addition to free cholesterol, the sterol can also be found esterified to various fatty acids
allowing it to be harmlessly stored as cytosolic droplets or in lipoprotein particles (LDLs).
Cholesterol can also be found esterified to a type of secreted polypeptide signaling molecule
encoded by the hedgehog gene family. In addition, cholesterol can be sulfated (cholesterol
sulfate) or glycosylated (cholesterol glucoside). Indeed, it seems cholesterol is one of those
molecules that nature really likes!
The cholesterol story offers an interesting conundrum. Cholesterol provides such a funda-
mentally essential role in the plasma membrane of animals that it would be easy to conclude
that cholesterol or a structurally similar molecule (eg.
-sitosterol or ergosterol) should be
essential for life, yet sterols are absent in prokaryotes and they are perfectly functional.
Also, in an animal cell, while the plasmamembrane is often essentially saturated in cholesterol,
the mitochondrial inner membrane is almost completely devoid of cholesterol! Without any
b
