166
chapter
10
Heteropolysaccharides I: Glycoproteins and Glycolipids
C arb o h y d ra te
Protein 4.1
S p ectrin dim er-
d im er ineraction
Glycophonn dimer
Protein 3 tetramer
Ankynn
Lipid bilayer
protein 4.1 interaction
F I G U R E 1 0 -1 3
Model of the organization of the red cell membrane skeleton. [Reproduced, with permission, from S. Lux and
S. B. Shohet, The erythrocyte membrane skeleton: Biochemistry.
H osp. P rac.
19 (1 0 ), 82 (1984). R. Margulies,
illustrator.]
fragmentation and loss of membrane as a result of circula-
tory and metabolic stresses and are selectively trapped and
removed by the spleen. In some kindreds with this disorder,
a qualitative defect in spectrin leads to poor binding with
protein 4.1 and to a weakened spectrin-protein 4.1-actin
complex. A spherocytic hemolytic anemia, having an auto-
somal recessive inheritance pattern associated with about
40% deficiency of the
a-
and ^-chains of spectrin, has
also been described. In hereditary elliptocytosis, the red
blood cells are elliptical. Molecular lesions identified in a
number of kindreds include deficiency of protein 4.1 and
diminished spectrin-spectrin or ankyrin-protein 3 inter-
actions. Both diseases are biochemically heterogeneous.
In
hereditary pyropoikilocytosis,
the isolated spectrin
seems incapable of forming higher oligomers (dimer-
dimer association)
in vitro,
possibly as a result of a
structural change in the a-subunit of spectrin. The red
cells show abnormal and bizarre shapes (poikilocytosis).
The cells hemolyze at a temperature 2-3° below that
(50°C) required to hemolyze normal cells. Normal spec-
trin melts (converts from ordered to disordered structure)
at 69°C.
Blood Group Antigens
Antigenic determinants (Chapter 35) known as
blood
group substances
are present on the surface of human red
blood cells. The blood group substances are inherited ac-
cording to Mendel’s law. Knowledge of blood group sub-
stances is essential for blood transfusion and valuable in
forensic medicine and anthropological studies. The anti-
gens are recognized by specific antigen-antibody interac-
tions that produce agglutination. For example, when red
blood cells containing a specific antigenic determinant
are mixed with plasma containing specific antibodies to
that antigen, cells will agglutinate through formation of
a network of antigen-antibody linkages. More than 100
different blood group antigens have been categorized on
the basis of their structural relationships into 15 indepen-
dent blood group systems. The blood group substances
are found on red blood cell membranes and in a variety of
tissue cells. Soluble blood group substances are found as
glycoproteins in saliva, gastric juice, milk, seminal fluid,
urine, fluids produced in ovarian cysts, and amniotic fluid.
The most widely investigated antigenic determinants
are the ABO and the Lewis blood group systems. The
antigenic specificities are established by carbohydrate
residues occurring at the nonreducing ends of oligosac-
charides of the glycoproteins and glycolipids (Table 10-4)
of red blood cell membranes.
The ABO blood group system is associated with three
antigens: A, B, and H. The specificity of these antigens
resides in difference of the terminal carbohydrate residue.
Addition of an N-acetylgalactosamine residue to an H anti-
gen yields an A antigen, whereas addition of a galactose
residue yields a B antigen (Table 10-4). The H antigen
itself is synthesized by addition of a fucosyl residue to a
