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chapter 19
Lipids II: Phospholipids, Glycosphingolipids, and Cholesterol
and subsequent isolation of the gene product has yielded
enough enzyme required for treatment (Chapter 23). Use
of the recipient’s erythrocytes in which the enzyme is en-
trapped is under investigation to minimize immunological
complications. Exposing erythrocytes to hypotonic con-
ditions in the presence of the enzyme causes formation
of pores in the membrane that allow rapid exchange of
the enzyme with the cellular contents. Restoration to iso-
tonicity reseals the membrane and entraps some of the
enzyme. Other enzyme carriers are liposomes, concen-
tric lipid bilayers prepared from cholesterol, lecithin, and
phosphatidic acid. The ideal treatment for these disor-
ders would be addition, or replacement, of genetic ma-
terial coding for the missing gene product. Replacement
therapy with a polyethylene glycol-modified form of the
missing enzyme, which has an extended half-life and
reduced immunogenicity, may provide a promising ap-
proach to treatment (see
Adenosine deaminase deficiency,
Chapter 27).
Alterations in Cell Surface Glycosphingolipids
Changes in cell surface glycosphingolipids occur during
fetal development and are reflected in several properties
of the cell, namely, receptor specificity, antigenic speci-
ficity, adhesion, and possibly cell growth regulation. Gly-
cosphingolipid metabolism is affected during oncogenic
transformation in cultured cells and may be responsible
for some properties of tumor cells (e.g., lack of contact
inhibition of growth).
19.3 Cholesterol
Cholesterol (3-hydroxy-5,6-cholestene) is a steroid and
contains
the carbon
skeleton
of cyclopentanoperhy-
drophenanthrene, which consists of three six-membered
rings and a five-membered ring. It is also a monohydrox-
yalcohol and contains a double bond between C
5
and
C(,:
Cholestanol
(dihydrocholesterol)
has
the
following
conformation:
In this structure, all of the ring fusions (between A and B,
B and C, and C and D) are trans, the hydrogen atoms or
methyl groups attached to the bridgehead carbons project
to opposite sides of the rings, and the rings are in the more
stable chair conformation. In cholesterol, the double bond
between C
5
and C
6
distorts the conformation of the rings
A and B and leads to the conformation shown below:
The angular methyl groups at Cig and C
1 9
, the 3-hydroxyl
group, and the side chain at C
17
all project toward the same
side of the ring system. These substituents are indicated
by solid lines and designated as /3. A substituent group
situated below the plane of the ring is in the «-orientation
and is indicated with a dotted line. In general, the an-
gular methyl groups are /3-oriented, but the 3-hydroxyl
group may be present in either the
a-
and ^-orientation.
In cholesterol, the 3-OH is in the ^-orientation.
In
some
naturally
occurring
compounds
(e.g.,
/1-coprostanol), the junction between rings A and B is cis.
This compound occurs in large quantities in feces, where
it is produced from cholesterol by action of the intestinal
flora.
Adults normally synthesize approximately 1 g of choles-
terol and consume about 0.3 g/day. Dietary cholesterol
is primarily derived from foods of animal origin such as
