Proteoglycans: Biological Roles and Strategies
343
and processes (Karamanos 1997), which are summarized in Fig. 24.1. For further
information on structure and function of PGs the excellent reviews of Khellen
and Lindahl 1991, Hascall et al. 1994 and Iozzo 1997 are recommended.
PGs are named according to their respective protein core and they form a heterogeneous group of glycoconjugates that are either components of the extracellular matrix or associated with the cell membrane or even as storage macromolecules in cytoplasmic granules (Khellen and Lindahl 1991). Studies on their structures and interactions with other effective molecules revealed their in vivo
importance and the results may trigger the development of new powerful pharmaceuticals and enhanced diagnostic techniques for various diseases. Apart from
their protein part, complex-carbohydrate structures and particularly the glycosaminoglycans (GAGs) give unique properties to PGs. Via their GAG chains PGs
interact with growth factors and growth factor receptors and participate in the
regulation of cell proliferation and differentiation as well as in matrix synthesis.
The effects of GAG constituents on these issues have been recently elucidated for
human malignant mesothelioma cells (Tzanakakis et al. 1995 and 1997, Syrokou
et al. 1999). To understand, therefore, in depth the mechanisms of PGs action as
well as their involvement in life processes, the fine chemical structures of their
carbohydrate constituents should be fully elucidated. The improvement in technology has helped scientists to develop strategies useful to determine PG composition and to elucidate their structure and interactions even when very low
amount of PGs (a few Ilg) are available. In spite of the ever increasing knowledge
of molecular biology which is helpful in characterizing the different protein cores
of PGs, there is still a long way to go when elucidating the fine structure of GAGs!
PGs and the biological functions driven from their complex-carbohydrate moieties (Karamanos and Hjerpe 1996).
3
Proteoglycans
PGs are considered to be one of the major family of structural glycoconjugates.
They constitute a separate family from that of glycoproteins since PGs are highly
charged macromolecules consisting of GAG and oligosaccharide chains covalently
bound to a protein core. With the exception ofhyaluronan (HA), all GAGs are synthesized as PGs. A representative model of a PG monomer is given in Fig. 24.2.
3.1
Glycosaminoglycans: Structure, Biosynthesis and Linkage to Protein
GAGs are linear polymers consisting of repeating disaccharide units that contain
one hexosamine (glucosamine or galactosamine) and one uronic acid (glucuronic and!or iduronic acid) or galactose in the case ofkeratan sulfate. The definition of the various GAG types is based on the type of these monosaccharides and
the glycosidic bonds between them (Figs. 24.3-5). There are four groups of
GAGs:
(1) hyaluronic acid or hyaluronan with [~4GlcAf31~3GlcNAcf31~1 as repeating
disaccharide unit,
343
and processes (Karamanos 1997), which are summarized in Fig. 24.1. For further
information on structure and function of PGs the excellent reviews of Khellen
and Lindahl 1991, Hascall et al. 1994 and Iozzo 1997 are recommended.
PGs are named according to their respective protein core and they form a heterogeneous group of glycoconjugates that are either components of the extracellular matrix or associated with the cell membrane or even as storage macromolecules in cytoplasmic granules (Khellen and Lindahl 1991). Studies on their structures and interactions with other effective molecules revealed their in vivo
importance and the results may trigger the development of new powerful pharmaceuticals and enhanced diagnostic techniques for various diseases. Apart from
their protein part, complex-carbohydrate structures and particularly the glycosaminoglycans (GAGs) give unique properties to PGs. Via their GAG chains PGs
interact with growth factors and growth factor receptors and participate in the
regulation of cell proliferation and differentiation as well as in matrix synthesis.
The effects of GAG constituents on these issues have been recently elucidated for
human malignant mesothelioma cells (Tzanakakis et al. 1995 and 1997, Syrokou
et al. 1999). To understand, therefore, in depth the mechanisms of PGs action as
well as their involvement in life processes, the fine chemical structures of their
carbohydrate constituents should be fully elucidated. The improvement in technology has helped scientists to develop strategies useful to determine PG composition and to elucidate their structure and interactions even when very low
amount of PGs (a few Ilg) are available. In spite of the ever increasing knowledge
of molecular biology which is helpful in characterizing the different protein cores
of PGs, there is still a long way to go when elucidating the fine structure of GAGs!
PGs and the biological functions driven from their complex-carbohydrate moieties (Karamanos and Hjerpe 1996).
3
Proteoglycans
PGs are considered to be one of the major family of structural glycoconjugates.
They constitute a separate family from that of glycoproteins since PGs are highly
charged macromolecules consisting of GAG and oligosaccharide chains covalently
bound to a protein core. With the exception ofhyaluronan (HA), all GAGs are synthesized as PGs. A representative model of a PG monomer is given in Fig. 24.2.
3.1
Glycosaminoglycans: Structure, Biosynthesis and Linkage to Protein
GAGs are linear polymers consisting of repeating disaccharide units that contain
one hexosamine (glucosamine or galactosamine) and one uronic acid (glucuronic and!or iduronic acid) or galactose in the case ofkeratan sulfate. The definition of the various GAG types is based on the type of these monosaccharides and
the glycosidic bonds between them (Figs. 24.3-5). There are four groups of
GAGs:
(1) hyaluronic acid or hyaluronan with [~4GlcAf31~3GlcNAcf31~1 as repeating
disaccharide unit,