close

Вход

Забыли?

вход по аккаунту

?

Biogenic Macromolecules of Arterial Tissue and Cartilage.

код для вставкиСкачать
C O N F E R E N C E REPORTS
Biogenic Macromolecules of Arterial Tissue and
Cartilage
By Eckharf Buddecke‘‘]
Proteoglycans are structural components of cells, of pericellular structures, and of the extracellular space in connective tissue. They have the chemical structure of graft
polymers, in which polysaccharide chains are covalently
linked to a central protein or polypeptide core. Chondroitin sulfate (CS),dermatan sulfate (DS),heparan sulfate,
and keratan sulfate have been identified as polysaccharide
components of proteoglycans of arterial tissue and cartilage.
Hyaline cartilage contains up to 40% of its dry weight of a
proteoglycan whose carbohydrate content amounts to 84%
and whose polysaccharide chains consist mainly of chondroitin sulfate [(1-4)P GlcUA (I-3)GalNAc 4-sulfate1,
bonded P-glycosidically to serine residues of the protein
through the trisaccharide galactosylgalactosylxylosyl.Light
scattering and viscosity measurements revealed a molecular weight of 0.5 x l o 6 to 1.0 x lo6, the molecular shape
of a stretched coil, a radius of gyration of 1400 A,and an
effective hydrodynamic volume of 20WOO ml of water
per g. These figures were confirmed by electron micrographs showing an ellipsoidal molecular shape with a
central protein filament of 180&2000 A length and 22
side chains of 520 8, length.
In a hybrid proteoglycan of arterial tissue, CS and DS are
components of the same macromolecule and are present
in part as copolymeric polysaccharide chains. The copolymeric structure of the polysaccharide chains was
proved by isolation of a tetrasaccharide having the structure GlcUA-GalNAc sulfate-IdUA-GalNAc
sulfate.
On incubation of arterial tissue in vitro in the presence of
35S-sulfateor ‘‘C-glucose, the 35Sor 14C was incorporated
into the polysaccharide chains at a constant rate for at
least 6 h ; however, the specific radioactivity of the ester
sulfate or iduronic acid groups of the DS is found to be
2-3 times greater than that of the ester sulfate or glucuronic
acid groups of CS.
The chemical and metabolic heterogeneity of the polysaccharide chains of the hybrid CS-DS protein of arterial
tissue is explained by the fact that biosynthesis of the carbohydrates is not subject to direct genetic coding but is controlled indirectly by the specificity and activity of the glycosy1 transferases, by the substrate concentration, and by
compartmenting of the pool of metabolic precursors. The
metabolic heterogeneity of the copolymeric CS-DS chains
is not in accordance with the generally assumed stepwise
synthesis of the carbohydrate side chains of the proteoglycan molecules.
Their physicochemical properties enable the proteoglycans
to bind water and Ca2+. Further, in model experiments
a “molecular sieve effect” could be observed : In solutions
of critical concentration, proteoglycans form a gel-like
macromolecular structure. Such systems are permeable to
small molecules (glucose, amino acids) but inhibit the
[*I
Prof. Dr. E. Buddecke
Institut fur Physiologische Chernie der Universitat
44 Munster. Waldeyerstrasse 15 (Germany)
Angew. Chem. inrernat. Edit. 1 Vol. 12 (1973) 1 N o . 1
passage of larger molecules. In vivo this “molecular sieve
effect” may be involved in control of extracellular and
pericellular transport processes.
Lecture at Darmstadt on June 16, 1972 [VB 351 IE]
German version: Angew. Chem. 85.94 (1973)
Chemical Structure and Biological Action of the
Components of Bee Venom
By E. Haberrnann“’
Bee venom contains three types of active ingredient :
1. Histamine is the most important of the biogenic amines.
It causes pain, dilates the blood vessels, and increases their
permeability.
2. A group of biologically active peptides is responsible for
the local and general toxicity of the venom. To this group
belong :
a) Melittin, whose primary structure is
GIy-Ile-Gly-Ala-Val-Leu-L
ys-Val-Leu-Thr-Thr-GI y-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-L
ys-Arg-Lys-Arg-Gln-GlnNH
The extremely irregular distribution of its amino acid
residues is remarkable. Mainly hydrophobic or slightly
hydrophilic neutral groups occupy the positions 1 to 20
while the C-terminal portion is strongly basic and wholly
hydrophilic. This structure resembles that of an invert
soap. Both the hemolytic potency of melittin and its ability
to lower the surface tension of water might be explained
by its primary structure. This is in accord with the almost
universal action of melittin on biological structures (cell
membranes, mitochondria, lysosomes, liposomes) and on
pharmacological test objects (smooth and striated muscle,
neuromuscular junction, sensible nerve endings, tonus and
permeability of blood vessels). Since mellitin constitutes
about 50% of dried bee venom, this peptide can be considered as the principal toxin.
b) Apamin (2 to 4% of dried venom). Its sequence is
C ys-Asn-C
ys-L ys-Ala-
Pro-Glu-Thr-Ala-Leu-C
ys
-Ala-Arg-Arg-Cys-Gln-Gln-HisNH2
The four half-cystines exist in the disulfide form. Unlike
the action of melittin, that of apamin is highly specific, in
that it augments the spinal polysynaptic reflexes. In mice
its action lasts for several days (LD,, : 4 to 5 mg/kg).c) MCD peptide (2 to 4% of the whole venom) degranulates
rat mast cells. The histamine released lowers the blood
pressure and dilates the blood vessels.
3. Enzymes. a) The structure and mode of action of bee
uenom phospholipase A has been determined recently by
[*] Prof. Dr. E. Habermann
Pharrnakologisches Institut der Universitat
63 Giessen, Schubertstrasse 1 (Germany)
83
Документ
Категория
Без категории
Просмотров
1
Размер файла
124 Кб
Теги
macromolecules, tissue, cartilage, biogenic, arterial
1/--страниц
Пожаловаться на содержимое документа