1. Metabolism of non-glucose carbohydrates
Learning objectives:
Discuss catabolism of mannose, fructose, and galactose
Discuss synthesis of lactose, glucosaminoglycans, and glycoproteins

2. Mannose C-2 epimer of glucose. Minor component of human diet.
Important component of glycoproteins.
CH2OH
CH2OPO32- O H OH O
Hexokinase H H H H
+ ATP
+ ADP
OH OH
OH OH OH H OH OH
H H
H H
Mannose Mannose 6-phosphate

3. Glycolytic pathway CH2OPO32- Phosphomannose isomerase CH2OPO32- O H H
CH2OH O H
OH OH
H OH OH OH H OH
H H
OH H
Mannose 6-phosphate Fructose 6-phosphate
Glycolytic
pathway

4. Fructose
Significant component of human diet, as a dietary monosaccharide
(e.g. from high-fructose corn syrup), or generated by hydrolysis of sucrose.
CH2OH
CH2OH O
H OH H OH
OH H
Fructose enters cells through transporter proteins, in particular
GLUT5 which is a fructose-specific transporter

5. In the liver and kidney (tissues other than liver) CH2OPO32- CH2OH
Hexokinase
CH2OH O
+ ATP ADP
H OH
H OH H OH H OH
OH H
OH H
+ ATP
Fructose Fructose 6-phosphate
Fructokinase
CH2OH-
CH2OPO32- O
In the liver
and kidney
H OH
+ ADP H OH
OH H
Fructose 1-phosphate

6. Liver fructose catabolism
CH2OPO32- Ι
C = O
HO – C – H
H – C – OH
CH2OH
Fructose 1-phosphate
Aldolase B
CH2OPO32- Ι
C = O
CH2OH
Dihydroxyacetone
phosphate
CHO Ι
H – C – OH
CH2OH
Glyceraldehyde
Glycolysis
CH2OPO32- Ι
C = O
HO – C – H
H – C – OH
Fructose 1,6-bisphosphate
Aldolase (A)
CH2OPO32- Ι
C = O
CH2OH
Dihydroxyacetone
phosphate
CHO Ι
H – C – OH
CH2OPO32-
Glyceraldehyde
3-phosphate

7. Glyceraldehyde kinase
CHO Ι
H – C – OH
CH2OPO32-
Glyceraldehyde
3-phosphate
CHO Ι
H – C – OH
CH2OH
Glyceraldehyde
+ ATP ADP

8. Glycolytic pathway Hexokinase Hexokinase/ Hexokinase Glucokinase
Mannose
Glucose
Fructose
Hexokinase Hexokinase/ Hexokinase
Glucokinase
Mannose 6-phosphate
Glucose 6-phosphate
Fructokinase
Phosphoglucose
isomerase
Phosphomannose
isomerase
Fructose 6-phosphate
Phosphofructokinase
Fructose 1,6-bisphosphate
Fructose 1-phosphate
Aldolase A Aldolase B
Glyceraldehyde 3-phosphate
Dihydroxyacetone phosphate
Glyceraldehyde
Glycolytic
pathway
Triose phosphate
isomerase
Glyceraldehyde kinase

9. ATP balances for converting monosaccharides into pyruvate
Glucose:
1 ATP spent in phosphorylating glucose to glucose 6-phosphate
1 ATP spent in phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate 1 2 x 1 ATP generated in the phosphoglycerate kinase step
2 x 1 ATP generated in the pyruvate kinase step
Mannose:
1 ATP spent in phosphorylating mannose to mannose 6-phosphate
1 ATP spent in phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate
2 x 1 ATP generated in the phosphoglycerate kinase step
Fructose in liver:
1 ATP spent in phosphorylating fructose to fructose 1-phosphate
1 ATP spent in phosphorylating glyceraldehyde to glyceraldehyde 3-phosphate
Fructose in other tissues:
1 ATP spent in phosphorylating fructose to fructose 6-phosphate
1 molecule of glucose, mannose, or fructose
converted to pyruvate yields 2 molecules of ATP

10. Galactose C-4 epimer of glucose
Significant component of human diet as part of the lactose in milk
CH2OH O OH OH H
OH H H H
H OH

11. CH2OH
CH2OH O OH OH O
Galactokinase OH H H H
+ ATP
+ ADP
OH H
OH H H H H
OPO32-
H OH
H OH
Galactose Galactose 1-phosphate

12. + + CH2OH CH2OH O O OH H H H H H O O O- O- OH H OH H H OPO32- OH
O – P – O – P – O - uridine
H OH
H OH
Galactose 1-phosphate
UDP-glucose
Galactose 1-phosphate
uridyl transferase
CH2OH
CH2OH- O OH H O H H H
O O
O O- H
OH H +
OH H H
O – P – O – P – O - uridine OH
OPO32-
H OH
H OH
UDP-galactose
Glucose 1-phosphate

13. CH2OH O OH H H
O O
O O-
OH H H
O – P – O – P – O - uridine
H OH
UDP-galactose
UDP-galactose
4-epimerase
CH2OH O H H H
O O
O O-
OH H OH
O – P – O – P – O - uridine
H OH
UDP-glucose

14. Sum of last two reactions:
Galactose 1-phosphate + UDP-glucose → Glucose 1-phosphate + UDP-galactose
UDP-galactose → UDP-glucose
__________________________________________________________________
Galactose 1-phosphate → Glucose 1-phosphate
Finally:
CH2OH
Phosphogluco-
mutase
CH2OPO32-
Glycolytic
pathway O H H O H H H H
OH H
OH H OH
OPO32- OH OH
H OH
H OH
Glucose 6-phosphate
Glucose 1-phosphate

15. Sum of all reactions:
Galactose + ATP → Glucose 6-phosphate + ADP
ATP balance for converting galactose into pyruvate
Galactose:
1 ATP spent in phosphorylating galactose to galactose 1-phosphate
1 ATP spent in phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate 1 2x 1 ATP generated in the phosphoglycerate kinase step
2 x 1 ATP generated in the pyruvate kinase step
1 molecule of galactose converted to pyruvate
yields 2 molecules of ATP

16. Lactose synthesis + A B Occur in the endoplasmic reticulum
Catalyst is composed of
β-D-Galactosyltransferase (Protein A, which has wide tissue distribution)
α-Lactalbumin (Protein B, which is only found in lactating mammary glands)
CH2OH
CH2OH O O OH H H OH H H
O O
O O- +
OH H
OH H H
O – P – O – P – O - uridine OH H
H OH
H OH
UDP-galactose Glucose
CH2OH
CH2OH
β-1,4
linkage
UDP-galactose:glucose
galactosyltransferase O O OH H OH H H O
OH H
OH H A B H H H
Lactose
H OH
H OH

17. + A N-acetyllactosamine synthesis (in glycoproteins)
Catalyst is composed of
β-D-Galactosyltransferase (Protein A, which has wide tissue distribution)
without protein B
CH2OH
CH2OH O O OH H H OH H H
O O
O O- +
OH H
OH H H
O – P – O – P – O - uridine OH H
H OH
H HN-COCH3
UDP-galactose N-acetyl-glucosamine
CH2OH
CH2OH
β-1,4
linkage O O OH H OH H H O
OH H
OH H A H H H
N-acetyllactosamine
H OH
H HN-COCH3

18. Synthesis of amino sugars
CH2OPO32-
CH2OPO32- O
CH2OH H OH O
Aminotransferase H
H OH
OH H H OH OH H
OH H
Glutamine Glutamate
H NH2
Fructose 6-phosphate Glucosamine 6-phosphate

19. Synthesis of acidic sugars
CH2OH O H H H
O O
O O-
OH H OH
O – P – O – P – O - uridine
H OH
UDP-glucose
2 NAD+ + H2O
2 NADH + 2 H+
UDP-Glucose
dehydrogenase
COOH O H H H
O O
O O-
OH H OH
O – P – O – P – O - uridine
H OH
UDP-glucuronic acid

20. Synthesis of oligo- and polysaccharides occur via “activated” sugar nucleotides
like UDP-galactose, UDP-glucuronic acid, or UDP-N-acetyl-galactosamine.
Glycosyltransferases catalyze the reactions. .