of their lysine residues. In diabetics, this process occurs
twice as often as in normal individuals of comparable age.
Lens cells, like red blood cells, do not require insulin for
the inward transport of glucose. However, the extent of
nonenzymatic glycation of crystallins is much lower than
that of hemoglobin (about 2.4% versus 7.5% at age 50)
because
1. The lens cells contain about one sixth the glucose of
red cells.
2. The content of lysine is lower in crystallin compared
to hemoglobin
3. The lysine residues are inaccessible in crystallins
owing to the high content of /
1
-pleated sheet
structures packed in a structured array oriented
orthogonally to the lens optic axis, restricting
rotational and translational movement. Crystallins
contain almost no a-helix, whereas hemoglobin, a
globular protein, possesses a high content of a-helical
structure and can freely rotate in the fluid media,
exposing the lysine residues.
Crystallins constitute 90% of the soluble proteins of the
lens cells (also called
fiber cells).
The human lens, a trans-
parent, biconvex, elliptical, semisolid, avascular structure,
is responsible for focusing the visual image onto the retina.
The lens grows throughout life at a slowly decreasing
rate, building layer upon layer of fiber cells around a cen-
tral core and never shedding the cells. Crystallin turnover
is very slow or nonexistent. In addition to nonenzymatic
glycation, crystallins undergo other age-dependent, post-
translational modifications
in vivo:
formation of disul-
fide bonds and other covalent cross-links, accumulation
of high-molecular-weight aggregates, deamidation of as-
paragine and glutamine residues, partial proteolysis at
characteristic sites, racemization of aspartic acid residues,
and photo-oxidation of tryptophan. Some of these pro-
cesses contribute to the increasing amount of insoluble
crystallins during aging. Nonenzymatic incorporation of
carbohydrates into proteins
in vivo
can be extensive and
may contribute to the pathophysiology of diabetes mellitus
and galactosemia.
10.2 Cell Membrane Constituents
Various aspects of the cell membrane are discussed
throughout this text, and a brief introduction is presented
here. The living system’s ability to segregate from and pro-
tect itself against—and interact with and against—changes
in the external environment is accomplished by mem-
branes. In the body, membranes function at the level of
156
tissues, cells, and intracellular domains. They function as
protective barriers and as transducers of extracellular mes-
sages carried by the chemical agents because they have
recognition sites that interact with metabolites, ions, hor-
mones, antibodies, or other cells in a specific manner. This
characteristic selectivity of membranes to interact with
specific molecules confers unique properties on a given
cell type. Within the cell, the membranes of organelles
are highly differentiated and have properties consistent
with metabolic function. Examples include electron trans-
port and energy conservation systems in the mitochondrial
membrane, protein biosynthesis in the rough endoplasmic
reticulum, modification and packaging of proteins for ex-
port in the membranes of the Golgi complex, drug detox-
ification in the smooth endoplasmic reticulum, and light
reception and transduction in the disk membranes or reti-
nal cells.
The membrane constituents are lipids (phospholipids,
glycosphingolipids, and cholesterol; Figure 10-5), carbo-
hydrates, and proteins. The ratio of protein : lipid : carbo-
hydrate on a weight basis varies considerably from mem-
brane to membrane. For example, the human erythrocyte
membrane has a ratio of about 49:43:8, whereas myelin has
a ratio of 18:79:3. The composition of the normal human
erythrocyte membrane is shown in Table 10-2. All mem-
brane lipids are
amphipathic
(i.e., polar lipids). The polar
heads of the phospholipids may be neutral, anionic, or
dipolar. The surface of the membrane bears a net negative
charge. The distribution of lipid constituents in the bilayer
is asymmetrical. For example, in the erythrocyte mem-
brane, phosphatidylethanolamine and phosphatidylserine
are located primarily in the internal monolayer, whereas
phosphatidylcholine and sphingomyelin are located in the
external monolayer.
Lipids are organized in bilayers that account for most
of the membrane barrier properties. Membrane proteins
may be
peripheral
(extrinsic) or
integral
(intrinsic). Pe-
ripheral proteins are located on either side of the bilayer
and are easily removed by ionic solutions, whereas inte-
gral proteins are embedded in the bilayer to varying de-
grees (Figure 10-6). Some integral proteins penetrate the
bilayer and are exposed to both external and internal en-
vironments. By spanning both external and internal envi-
ronments of the cell, these proteins may provide a means
of communication across the bilayer that may be useful
in the transport of metabolites, ions, and water, or in the
transmission of signals in response to external stimuli pro-
vided by hormones, antibodies, or other cells. Because
of hydrophobic interactions, isolation of integral pro-
teins requires harsh methods, such as physical disruption
of the bilayer and chemical extraction procedures using
chapter
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Heteropolysaccharides I: Glycoproteins and Glycolipids
