Chemistry Reference
In-Depth Information
in man, with constitutive expression of GLT25D1, while GLT25D2 is limited to
nervous tissue.
7.3
Regulation of
O
- Glycosylation and Glycan Processing
The biosynthesis and processing for the different families of protein- linked glycans
is quite different, and refl ects the discrete regulation of structure and biological
function.
O
-Glycan chains are formed due to the concerted action of specifi c gly-
cosyltransferases, and the specifi city of the transferases determines the fi nal struc-
ture of the glycans and explains the glycoform diversity seen in proteins.
Both biosynthesis and processing of
O
-glycans by glycosyltransferases and gly-
cosidases takes place in the ER and Golgi apparatus. The
O
- glycans are formed
and processed in stepwise sequential fashion. The different types of
O
- glycosyl-
ation show their own characteristic manipulations in this respect. The formation
and processing of
O
-glycans is regulated at the level of gene expression, mRNA
and enzyme protein activity. Additional control exists through substrate and
cofactor concentrations at the subcellular site of synthesis. These processes are
integrated to create and regulate the huge variety of glycan structures utilized by
different species, tissue and cell types, and observed in different states of develop-
ment and differentiation. Table 7.5 summarizes the major points concerning the
regulation of
O
- glycosylation.
Table 7.5
Regulation of metabolic routes.
Level of regulation
Specifi c targets
Intermediary metabolism
Substrates
Acceptor: protein, glycoprotein
Donor: nucleotide sugar
Intermediary metabolism
Substrate availability
Nucleotide and nucleotide sugar transporters
Cellular and subcellular
Glycan processing
Protein synthesis and expression
Proteolytic processing
Subcellular localization of proteins
Developmental expression
Immune cell expression and response
7.3.1
O
- G al NA c , Mucin Type
In terms of glycan processing, the Ser (Thr)-GalNAc class of
O
- glycans is assem-
bled through the action of a series of linked biosynthetic pathways located in
regions of the ER and Golgi apparatus [2]. The pathways lead to predictable struc-
tures with core, backbone and peripheral units that are found linked to specifi c
