Environmental Engineering Reference
In-Depth Information
of HS biosynthetic enzymes [15]. The biosynthesis of HS is accomplished by a
complex pathway involving backbone elongation and multiple modification steps
(Fig. 2). HS biosynthesis takes place in the lumen of the Golgi apparatus, although
the core protein is biosynthesized in the endoplasmic reticulum (ER). The biosyn-
thesis of HS is initiated as a copolymer of GlcUA and GlcNAc of which the
polymer formation is catalyzed by copolymerases (EXT1 and EXT2) [14]. The
backbone is then modified by a C
5
-epimerase and different sulfotransferases. The
first modification is
N
-deacetylation/
N
-sulfation to form the
N
-sulfo glucosamine
unit (GlcNS) by
N
-deacetylase/
N
-sulfotransferase (NDST). NDST is a dual func-
tion enzyme that catalyzes the removal of the acetyl group from a GlcNAc
residue and the transfer of a sulfo group to the amino group of the result-
ing GlcNH
2
. NDST has four different isoforms which have different types of
OH
HOOC
O
O
O
O
HS backbone
HO
HO
O
OH
NHAc
NDST
OH
OH
NDST
O
O
O
O
N
-sulf ated backbone
HO
HO
O
O
NHSO
3
-
NHAc
Epi, 2OST
HO OC
HO OC
HOOC
O
O
2-
O
-sulf ated HS
O
O
OH
O
OH
Epi
2OST
O
HO
O
O
O
OH
HO
-
O
3
SO
OSO
3
-
OH
6OST
6OST
O
O
O
O
HO
HO
6-
O
-sulf ated HS
O
O
NHSO
3
-
NHSO
3
-
3OST
OSO
3
-
OSO
3
-
3OST
O
3-
O
-sulf ated HS
O
O
O
-
O
3
SO
O
HO
O
NHSO
3
-
NHSO
3
-
Fig. 2
HS modification pathway. Synthesis is initiated as a copolymer of GlcUA and
GlcNAc by D-glucuronyl and
N
-acetyl-D-glucosaminyltransferase. The first modification is to
form the
N
-sulfo glucosamine unit (GlcNS) by
N
-deacetylase/
N
-sulfotransferase (NDST). The
C
5
-epimerase then converts the neighboring GlcUA on the reducing side to an IdoUA unit. The
chain modification proceeds with 2-
O
-sulfation at the iduronic acid (or to a lesser extent at a
GlcUA), 6-
O
-sulfation at the glucosamine, and 3-
O
-sulfation at the glucosamine by different
O
- sulfotransferases. The reactions involved in polymer elongation steps are not shown
Search WWH ::
Custom Search