Chemistry Reference
In-Depth Information
are responsible for this diversifi cation process (Figure 6.5): (i) trimming
-
mannosidases, (ii) nucleotide sugar transporters, (iii) glycosyltransferases, and (iv)
sulfotransferases and
O
- acetylases.
α
6.6.1
Golgi Mannose Trimming as the Start for
N
- Glycan Elongation
The two Golgi apparatus- located
1,3/6 -
mannosidases MA2A1 (Q16706) and MA2A2 (P49641) remove B- and C-branch
mannoses to enable the synthesis of complex-type
N
- glycans. Both mannosidases
II are able to remove
neutral
mannosyl - oligosaccharide
α
- tetramannosyl struc-
tures. This trimming initiates the formation of complex- type
N
- glycans. It strongly
depends on prior addition of the A-branch GlcNAc by
N
- acetylglucosaminlytrans-
ferase-I (see below). Both
α
1,3 - and
α
1,6 - linked mannoses from 6
′
-mannosidases are equally and constitutively expressed
in human tissues. Defi ciency of MA2A1 activity as observed in HEMPAS (heredi-
tary erythroblastic multinuclearity with positive acidifi ed serum lysis test) patients
(congenital dyserythropoietic anemia type II) can be compensated by MA2A2, but
only with a substantial loss of
N
-glycan diversity (please see also Table 23.1).
α
6.6.2
Nucleotide Sugar Transporters Import the Fuel for Oligosaccharide Elongation
Nucleotide sugar transporter s (NSTs) and sulfate (3
-
phosphosulfate, PAPS) transporters are solute carriers that import activated donor
substrates for glycan elongation reactions into the secretory pathway. They are
polytope membrane proteins that are targeted by short cytosolic amino acid
sequences to their accurate location. For instance, ER- resident UDP - Glc trans-
porter (S35B1) is retrieved by its cytosolic COPI-binding motif (KKTSH), whereas
′
- phosphate adenosine 5
′
Figure 6.5
Illustration of the biosynthetic
pathway leading to the synthesis of complex-
type
N
-glycans. (a) Enzymes are named accord-
ing to their primary entry name in Swiss-Prot
(www.expasy.org). Enzymatic reactions (arrows)
are named according to the enzyme commis-
sion (www.brenda.org). Activated sugar nucle-
otides serve as donor and the preformed
N
-glycan precursors as acceptor substrates for
glycosyltransferase reactions. (b) Detailed view
of all reactions needed for accurate addition of
N
-acetylglucosamine by MGAT5 is shown
(dashed box B in C). Catalysis of the reverse
reaction (dotted arrow) that is entropically
favored is inhibited by the effi cient removal of
liberated UDP. UDP-UMP conversion by the
different human ectonucleoside diphospha-
tases is coupled to the immediate export of
UMP out of the Golgi apparatus lumen by the
solute carriers mentioned in the right box in B.
(c) Transferases are named in framed boxes
adjacent to the enzyme reaction catalyzed. The
gray scale of the frame was specifi cally chosen
and refl ects sugars transferred. Arrows in gray
point to additional distant linkages. The thick-
ness of the arrows for sialyltransferases repre-
sents relative specifi city towards different
positions. Numbers in bold refl ect preferred
linkage types. Transferases with dotted frames
depend on non-linear acceptor substrates
(dotted gray box). Different human sulfotrans-
ferases are listed with some features in the right
upper corner. In case of sulfation, only a few
possible linkage types with know function have
been illustrated.
