ESSENTIALS OF GLYCOBIOLOGY
LECTURE 4
MONOSACCHARIDE METABOLISM
AND SUGAR NUCLEOTIDE TRANSPORTERS
Hud Freeze
INTRODUCTION
•Traditional Approach--Study the enzymes and substrates in cells
•Holistic Approach--Add homeostasis and disease considerations
•Glucose is the central player, but not the only player
•Monosaccharides = sugars
First Principles
•Meet the players
•Source of sugars:
•Transport into cells
•salvage them
•make them in cells
•Activate the sugars
•Deliver activated sugars to the proper location
Xyl
GlcA
Sia
GlcNAc
GalNAc
Fuc
Gal
Glc
Glc
Man
Fru-6-P
THE SUGAR LEAGUE
THREE WAYS TO ACTIVATE A SUGAR
NTP PPi
1. Sugar + ATP
2. Sugar(A)-NDP
Sugar-P
Sugar-NDP
Sugar(B)-NDP
3. Sugar(A)-NDP + Sugar(B)-1-P
Sugar(B)NDP + Sugar(A)-1-P
Activated Sugar Donors
Sugar
Activated Form
Glc
Gal
GlcNAc
UDP-Sugar
GalNAc
GlcA
Xyl
Man
Fuc
Sia
GDP-Sugar
CMP-Sia
MONOSACCHARIDE TRANSPORTERS
Type
Primary Location
Km (Glucose)
(mM)
Ion Coupled
(Na+/glucose)
Epithelial C ells
SGLT 1
Small intestine
0.1 - 0.8
Some kidney
SGLT 2
Kidney co rtex
1.6
Facilitated diffusion
GLUT 1
Erythrocytes, blood tissue barrier
5
GLUT 2
Liver, small intestine
6-12
GLUT 3
Neurons, p lacenta
1-2
GLUT 4
Adipose tissue, skeletal muscl e,
insulin regulated
GLUT 5
Small intestine
GLUT 7
Microsomal ? Glc from ER
Man
Many cell types
Fuc
Several cell ty pes
5
6 (Fructose)
30-70 µM
(Mannose)
~250 µM (Fucose)
Isoform
Main Tissue Localization
Functional Characteristics
(Transport)
GLUT1
Erythrocytes, brain, ubiquitous
Glucose
GLUT2
Liver, pancreas, intestine, kidney
Glucose (low affinity); Fructose
GLUT3
Brain
Glucose (high affinity)
GLUT4
Heart, muscle, adipose tissue,
brain
Glucose (high affinity)
GLUT5
Intestine, testes, kidney
Fructose; Glucose (very low
affinity)
GLUT6
Brain, spleen, leucocytes
Glucose
GLUT7
n.d.
n.d.
GLUT8
Testes, brain and other tissues
Glucose
GLUT9
Liver, kidney
n.d.
GLUT10
Liver, pancreas
Glucose
GLUT11
Heart, muscle
Glucose (low affinity); Fructose
(long form)
GLUT12
Heart, prostate, muscle, small
intestine, adipose tissue
n.d.
GLUT13
Testes specific
n.d.
GLUT14
Brain
H+–myo–inositol
*
* GLUT11 occurs in two splice variants: a short from (low-affinity glucose transport and a long form (which may be a
fructose transporter).
Facilitated Diffusion Transporter Topology and Signature Motifs
N
GR
Y
G
w
G
G
P
GRK
Y
E
RG
PESPRYL
ERVGRR
PETKG
E
NH2
COOH
Human Hexose Facilitated Diffusion Transporters
SPECIFICITY NAME LOCALIZATION
GLUT1
erythrocytes, brain
GLUT4
muscle, fat, heart
GLUT3
brain, testis, ovary
GLUT14 testis
glucose/fructose
liver, islets
GLUT2
GLUT8
GLUT6
blastocysts, brain, testis
spleen, leukocytes, brain
GLUT10 liver, pancreas
H+-myo-inositol
fructose
GLUT12
heart, prostate
HMIT
brain
GLUT5
Intestine, testis, kidney
GLUT9
liver, kidney
GLUT11
heart, muscle
Figure 6: Mannose flux in cells.
M
*
ER
*
M
M
M
M
LYS
M
*
M
M
M
G
M
M
*
M
*
M
M
M
M
GDP-M
M
M
Gl6P
M1P
EXTRACELLULAR
FLUID
fructose
Gl
glucose
M1P
mannose-1-p
M6P
mannose-6-p
F6P
fructose-6-p
Gl6P
glucose-6-p
M
M
F
Gl
M
F
Gl
GUT
Gl
F
M
M
Gl
F F
Gl
M
distal modification
transport process
enzymatic activity
transporter
F6P
M6P
CELL
F
*
M
*
mannose
GDP-M GDP-mannose
protein
M
M
M
Gl
Evidence Favoring Carbohydrate Salvage Pathways
Amino Sugars

>50% of label reused for new glycoconjugates (GalNAc,
GlcNAc)

~70% of 3H-GlcNAc incorporated into sugar nucleotides
in rat liver

~30% of 3H-GlcN iv injected into rats is incorporated into
plasma glycoproteins

20-30% Sialic acids recycled in some cells

GlcNAc/ManNAc kinase present in many tissues

GalNAc-1-kinase distinct from Gal-1-kinase
Hexose and Fucose

Mannose transporter, uses physiological concentrations
of M annose

Cells lacking UDP-Gal-4-epimerase can use serum
OVERVIEW OF SUGAR METABOLISM IN CELLS
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Remember:
1. Glucose is central
2. Pathways not = in all cel
3. Map is 2-D, not 3-D
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
GlcNAc-l-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
Biosynthesis and Interconversion o f Monosaccharides. The relative contributions of
each und er phys iolog ical cond it ions are unknown.
- monos accharides;
-control points
and
- donors;
GTP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
GTP
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
Galactosemia is caused by a
Failure in Gal-1-P:UDP-Glc
Uridyl transferase
A. GDP-Man
GDP-Fuc - Three reactions, two enzymes: GDP-Man 4,6 dehydratase
and GDP-keto-6-deoxymannose 3,5 epimerase/4-reductase
GALACTOSE ACTIVATION USES ALL THE OPTIONS
GDP-(D)-mannose
GDP-4-keto, 6-deoxy (D)-mannose
CH2OH
O
O
OH HO
O
O
O
NADP H
GDP
GDP
CH3
O
OH HO
1. Sugar + ATP
NADP+
2. Sugar(A)-NDP
Sugar-P
O
CH3
HO
O
NADP H
OH
GDP
CH2OH
CH2OH
O
O
OH
H
H
+ NAD
H
O
OH
UDP-Glc
O
NADP+
OH
GDP
Sugar(B)NDP + Sugar(A)-1-P
UDP-Gal - Single enzyme: UDP-Gal-4-epimerase
B. UDP-Glc
HO
Sugar-NDP
GDP-keto-6-deoxy mannose
3,5 ep imerase/4-reductase
3. Sugar(A)-NDP + Sugar(B)-1-P
H
HO
OH
Sugar(B)-NDP
GDP-M an 4,6 dehy dratase
H
GDP-(L)-fucose
NTP PPi
CH3
O
HO
GDP-4-keto,
6-deoxy-(L)-glucose
UDP
NADH + H+ +O
H
OH
CH2OH
H
+ NAD
H
O
H
HO
UDP
OH
(4-keto intermediate)
H
O
H
H
OH
H
H
OH
O
UDP-Gal
UDP
GALACTOSE METABOLISM
Galactosemia
UDP-Glc + Gal-1-P X
Glc-1-P + UDP-Gal
Inability to metabolize Galactose--potentially lethal
Treatment: Galactose restricted diet
Even with proper diet: patients have dyspraxic speech, ovarian failure,
poor growth, neurological impairment
Knockout mouse does not have disease phenotype! Other genes important
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
GTP
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
Mannose supplements can treat a
human disorder: Fru-6-P-->Man-6-P
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
Biosynthesis and Interconversion o f Monosaccharides. The relative contributions of
each und er phys iolog ical cond it ions are unknown.
- monos accharides;
-control points
and
- donors;
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
GTP
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
Oral fucose supplements used to
treat a human genetic disorder
A. GDP-Man
GDP-Fuc - Three reactions, two enzymes: GDP-Man 4,6 dehydratase
and GDP-keto-6-deoxymannose 3,5 epimerase/4-reductase
GDP-mannose
GDP-4-keto,
6-deoxy-mannose
CH 2OH
GDP-4-keto,
6-deoxy-glucose
CH 3
O
O
O
+
NAD P
OH HO
HO
GDP-fucose
O
NAD PH
O
O
OH HO
CH 3
O
O
CH 3
HO
O
GDP
GDP-Man 4,6 dehydratase
OH
O
OH
NAD PH
GDP
GDP
GDP-keto-6-deoxymannose
3,5 epimerase/4-reductase
HO
+
NAD P
OH
GDP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
GTP
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
UDP-GlcNAc epimerase/kinase
Defective in two human diseases
Are the enzymes and substrates in the cytosol really “soluble”?
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
GTP
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Dol-P
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
Fru-6-P is the only freely soluble
glycolytic intermediate
If all the sugars can be inter-converted, how can you follow just one?
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Remains as [2-3H]Mannose
[2-3H]Man
PO4
PO4
OH
PMI
O
HO
HO
TRICKS OF THE TRADE
G6P
O
HO
HO
OH
3H
OH
OH
[2-3H]M6P
H2O
3HOH
F6P
PMM
[2-3H]M1P
Glycolysis
Glycoproteins
Remains as [4-3H]Galactose
UDP-Gal - Single enzyme: UDP-Gal-4-epimeras e
B. UDP-Glc
CH 2OH
H
HO
O
H
OH
H
CH 2OH
O
H
+ NAD
H
O
OH
UDP-Glc
UDP
NADH + H+ +O
H
OH
CH 2OH
H
+ NAD
H
O
H
HO
UDP
OH
(4-keto intermediate)
H
O
H
OH
H
H
OH
H
O
UDP-Gal
UDP
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
Some Control Points for Sugar Nucleotide Synthesis
Enzyme
Inhibitor
UDP-Glc dehydrogenase
UDP-Xyl
GDP-Man 4,6-dehyd ratase
GDP-Fuc
Glutamine:fructose-6-P acetyltransferase
UDP-GlcNAc
UDP-GlcNAc epimerase/kinase
CMP-Sia
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
GTP
?’s
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
These are the Major Leaguers, how about life in the Minors?
BIOSYNTHESIS OF UNUSUAL SUGARS
KDN--2-keto-3-deoxy-D-glycero-D-galactonononic acid
a sialic acid analog found mostly in fish eggs
Man--->Man-6-P---> KDN---> CMP-KDN
+
+
PEP
CTP
Glycoproteins, glycolipids
Galactofuranose--Galf, found in bacteria and lower eukaryotes
UDP-Galp---->UDP-Galf----> Glycoconjugates
mutase
Galactofuranosyl transferases
SYNTHESIS OF DOLICHYL PHOSPHATE
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
From: Schenk et al Glycobiol 11, 61R, 2001
All of the precursors are made in the cytoplasm or nucleus-BUT, most glycoconjugates are made in the Golgi or ER
Glycolysis
Gal
Glc
ATP
Man
GlcNAc
ATP
ATP
Pi
Gal-1-P
Glycogen
Glc-6-P
Man-6-P
Fru-6-P
NAD
UDP-Glc
NAD +
UDP-GlcA
GlcN-6-P
Glc-1-P
AcCoA
GTP
GlcNAc-6-P
GDP-Man
Dol-P
ATP
Man-l-P
Dol-P-Glc
NADP
-CO2
GlcNAc-l-P
GalNAc
GalNAc-1-P
Dol-P
GDP-Fuc
UTP
UDP-Xyl
ATP
Fuc-1-P
-NH3 Glutamine
UTP UDP-Glc
UDP-Gal
Fuc
UTP
Dol-P-Man
UDP-GalNAc
UDP- GlcNAc
ManNAc
ATP
CMP-Neu5Ac
ManNAc-6-P
PEP
NADP
CMP-Neu5Ac
CTP
Neu5Ac
Neu5Ac-9-P
GTP
: Nucleotide Transport in Golgi & ER
Nucleotide
ER
Golgi
CMP - Sia
-
+++
GDP - Fuc
-
++++
UDP - Gal
-
++++
PAPS
-
++++
GDP - Man
-
++++
UDP - GlcNAc
++
++++
UDP - GalNAc
++
++++
UDP - Xyl
++
++++
ATP
+++
++++
UDP - GlcA
++++
++++
UDP - Glc
++++
+
TRANSPORTERS IN THE GOLGI
Mammals
PAP S
AT P
Mammals
AMP o r
AD P
?
Pi
Leishmania
Mammals
Yeast
UDP-Galactos
e
Mammals, yeast
UDP N-Acetylglucosamin
e
Pi
Mammals
UDP N-Acetylgalactosamin
UMP -2
CMPSialic Aci d
CMP
Mammals
GMP
GDP-Fucos e
Mammals
GDPMannos e
Leishmania
Yeast
e
Mammals, Plants
UDP-Glucos e
UDP-Xylos e
Mammals
UDPGlucuronic Aci
d
Ma m m a l s
Freeze: 6.3
TRANSPORTERS IN THE ENDOPLASMIC RETICULUM
?
HOW IT WORKS
TRANSPORTERS: A FAMILY IN LOVE WITH ITS MEMBRANES
DONORS AND CARRIERS FOR GLYCAN MODIFICATIONS
MODIFICATION
Phosphate
Sulfate
Methyl
Acetyl
Pyruvate
Acyl
Succinyl
PRECURSOR
TRANSPORTER
ATP
PAPS
AdoMet
Acetyl-CoA
PEP
Acyl-CoA (?)
Succinyl-CoA (?)
Yes
Yes
?
Yes
?
?
?
SUMMARY AND TAKE HOME MESSAGES
Glucose can be made into all sugars (monosaccharides)
All sugars require activation and most require transport of the activated forms
Transporters deliver the sugars to cells
Salvaged and imported sugars can contribute to glycoconjugate synthesis
The relative contributions of each source may be cell/tissue specific
Some disorders in sugar metabolism can be treated with dietary modifications
Hard to know specificity of sugar nucleotide and monosaccharide transporters
Sugar is good for you---mostly