O lig o m an n o sid ic
• —
y '
H um an im m unoglobulin M
(IgM), b o v in e rh o d o p sin
C o m p lex
T -T ^
C h ick en o v album in,
S in d b is virus
In n er d o m ain
■ —A—• —▼
■—A—* —T'
H u m an a n d rabbit tran sferrin ,
rat liver p la sm a m e m b ra n e
-A—• —T-v
-A—• —Y''
V esicu lar sto m a titu s virus
I—A—• —
I—A—• —
H u m an im m unoglobulin G
(IgG )
I—A—• —T-s
A—• —Y''
B ovine im m unoglobulin G
(IgG )
F I G U R E 1 0 -3
N-Glycosidically linked oligosaccharides. The oligomannosidic type is
rich in mannose residues, whereas the complex type contains carbohydrate
residues in the outer domain. Both types have a common core.
A = galactose, ▼
= mannose, a = L-fucose, • =
N-acetylglucosamine, ■ = N-acetylneuramine acid. [Adapted, with
permission, from N. Sharon and H. Lis, Special Report,
C hem . E ng. N ew s,
p. 28 (March 30, 1981) © 1981 by the American Chemical Society.]
may be found in adjacent hydroxyamino acid residues, or
they may occur in close proximity, e.g., in glycophorin,
human chorionic gonadotropin, and antifreeze glycopro-
tein. This last is found in the blood of Arctic and Antarctic
fish species and other species on the eastern coast of North
A —
C o llag en
■ — □ —
O vine subm axillary m ucin
A n tifreeze g ly co p ro tein ,
A — □ —
h u m an im m unoglobulin A, (IgA,),
rat a n d rabbit brain gly co p ro tein s
■ — A — □ —
C alf fetuin, glycophorin,
h u m an chorionic g o n ad o tro p in
A+ porcine subm axillary m ucin
F I G U R E 1 0 -4
O-Glycosidically linked oligosaccharides. The sugar residues vary from
one to many and are not arranged in any particular pattern. A = Galactose;
= L-Fucose; □ = GalNAc; ■ = N-acetylneuraminic acid. [Adapted
with permission from N. Sharon and H. Lis, Special report,
C hem . Eng.
N e w s
, p. 28 (March 30, 1981). ©1981 by the American Chemical Society.]
America. It contains a very high amount of carbohydrate,
since every threonine residue of the glycoprotein is linked
with a galactosyl-/?-(l —> 3)-N-acetylgalactosamine unit.
The protein consists of the repeating tripeptide sequence
of alanyl-alanyl-threonine. The presence of antifreeze
glycoprotein, along with high concentrations of NaCl
in the blood, prevents water from freezing in blood
vessels and permits survival at the low temperatures
of polar seawater. This freezing-point depression by
antifreeze glycoproteins has been attributed to their
highly hydrated and expanded structure, which interferes
with the formation of ice crystals.
In all glycoproteins, the polypeptide component is syn-
thesized first on the membrane-bound ribosomes of the
rough endoplasmic reticulum; carbohydrate side chains
are added during passage through the endoplasmic retic-
ulum and Golgi apparatus. The carbohydrate additions
involve specific glycosyltransferases and their substrates
(uridine diphosphate sugars) and, in some glycoproteins,
an oligosaccharide carrier known as dolichol (a lipid). (See
also Chapters 16 and 25.)
Glycoproteins can also be formed by addition of car-
bohydrate residues without any of the complex enzymatic
pathways of carbohydrate addition. This process, known
as nonenzymatic glycation, proceeds by the condensation
of a monosaccharide, usually glucose, with certain reactive
amino groups on the protein. The initial, labile Schiff base
adduct slowly rearranges to the stable ketoamine or fruc-
tosamine form (Chapter 2). For example, a small fraction
of hemoglobin A, the major hemoglobin of adult humans,
is present in the red blood cells as glycated hemoglobin
(HbAic). The glycation of hemoglobin is a continuous
process occurring throughout the
1 2 0
-day life span of
the red cell. In HbAjc, glucose is incorporated via an
N-glycosidic linkage into the N-terminal amino group of
valine of each /3-chain. Enhanced levels of HbAlc occur in
individuals with diabetes mellitus (Chapter 22), and mea-
surement of glycated hemoglobin has been useful in moni-
toring the effects of therapy. Human serum albumin, which
has a half-life of 19 days, is also subjected to nonenzymatic
glycation, producing a stable condensation product known
as fructosamine. Fructosamine is a generic term applied
to the stable condensation product of glucose with serum
proteins, of which albumin is quantitatively the largest
fraction. Measurement of fructosamine concentration pro-
vides a means by which short-term (1-3 weeks) plasma
glucose levels can be estimated, whereas measurement of
HbAic concentration reflects integrated plasma glucose
levels over a longer period (2-3 months). Human lens pro-
a-, fi-,
and y-crystallins, which have much longer
life spans than other proteins in the body, also undergo age-
dependent, nonenzymatic glycation at the £-amino groups
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