METABOLISM OF GALACTOSE, FRUCTOSE & AMINO SUGARS

2. Gandham.Rajeev
Email:gandhamrajeev33@gmail.com

3. • Lactose, present in milk & milk products.
• Principal dietary source of galactose.
• Lactase ( β-galactosidase ) of intestinal
mucosal cells hydrolyses lactose to galactose
and glucose.
• Galactose is also produced from lysosomal
degradation of glycoproteins & glycolipids.

4. • Galactose is metabolised almost exclusively
by the liver and therefore galactose
tolerance test is done to assess the functional
capacity of the liver
• UDP-galactose is the active donor of
galactose during synthetic reactions

5. • Step: 1
• Galactokinase reaction:
• Galactose is first phosphorylated by
galactokinase to galactose -1- phosphate
• Step: 2
• Galactose -1- phosphate uridyl transferase
• This is the rate limiting enzyme.

6. • Galactose 1-phosphate reacts with UDP-
glucose to form UDP-galactose & glucose 1-
phosphate, in the presence of the enzyme
Galactose 1-phosphate uridyl transferase

7. • UDP-galactose is an active donor of galactose.
• UDP-galactose is essential for the formation of
compounds like lactose, glycosaminoglycans,
glycoproteins, cerebrosides & glycolipids.
• Step: 3
• Epimerase reaction:
• UDP-galactose can be converted to UDP-
glucose by UDP hexose 4-epimerase

8. • Galactose is channeled to the metabolism of
glucose.
• Galactose is not an essential nutrient since
UDP-glucose can be converted to UDP –
galactose by the enzyme UDP-hexose 4-
epimerase and requires NAD+
• Galactose is not essential in diet

9. • Step: 4
• Alternate pathway:
• The galactose 1-phosphate
pyrophosphorylase in liver becomes active
only after 4 or 5 years of life
• The enzyme will produce UDP-galactose
directly which can be epimerized to UDP-
glucose.

10. Galactose
Galactose 1-phosphate
Glucose 1-phosphate
Glucose 6-phosphate
Glycolysis Glucose
Galactitol
UDP-Glucose
UDP-Galactose
Lactose GAGS
Glycolipids
Glycoproteins
NADP
ATP
ADP
Galactokinase
Gala-1-Pho-Uridyl transferase
E
p
i
m
e
r
a
s
e
Mutase
Synthase
Galactose Metabolism

11. Disorders of galactose metabolism
• Classical galactosemia:
• Due to deficiency of enzyme galactose 1-
phosphate uridyltransferase
• Rare congenital disease in infants
• Inherited as an autosomal recessive disorder

12. Salient features
• Due to the block in this enzyme, galactose 1-
phosphate will accumulate in liver.
• This will inhibit galactokinase as well as
glycogen phosphorylase
• It results in hypoglycemia.
• Galactose cannot be converted to glucose
• Increased galactose level increases insulin
secretion, which lowers blood glucose level.

13. • Galactose metabolism is impaired leading to
increased galactose levels in circulation
(galactosemia) & urine (galactosuria)
• Bilirubin uptake is less & bilirubin conjugation
is reduced.
• Unconjugated bilirubin level is increased.

14. • There is enlargement of liver, jaundice &
severe mental retardation – due to
accumilation of galactose & galactose 1-
phosphate.

15. Galactosemia

16. Development of cataracts
• Causes:
• Excess of galactose in lens is reduced to galactitol
(dulcitol) by the enzyme aldose reductase
• Galactitol cannot escape from lens cells
• Osmotic effect of the sugar alcohol contributes to
injury of lens proteins & development of cataracts.

17. Galactokinase deficiency
• The defect in the enzyme galactokinase.
• Results in galactosemia & galactosuria
• Dulcitol or galactitol is formed.
• Absence of hepatic and renal complications.
• Development of cataracts very rare.
• Treatment:
• Removal of galactose & lactose from the diet.

18. Fructose metabolism
• Fructose is present in fruit juices & honey.
• Chief dietary source is sucrose.
• Sucrose is hydrolyzed in the intestine by the
enzyme sucrase.
• Fructose is absorbed by facilitated transport
and taken by portal blood to liver.
• It is mostly converted to glucose.

19. • Fructose is easily metabolized & a good
source of energy
• Seminal fluid is rich in fructose &
spermatozoa utilizes fructose for energy.
• In diabetics, fructose metabolism through
sorbitol pathway may account for the
development of cataract.

20. Fructose metabolism
• Fructose is phosphorylated to form fructose 6-
phospate, catalyzed by the enzyme
hexokinase
• Affinity of the enzyme hexokinase for
fructose is very low
Fructose Fructose -6-p Glucose-6-p
E.M pathway
ATP ADP
Hexokinase Isomerase

21. • Fructose is mostly phosphorylated by
fructokinase to fructose-1-phosphate
• Fructokinase is present in liver, kidney,
muscle and intestine.
• Hexokinase can also act on fructose to
produce fructose 1-phosphate.

22. • Fructose-1-phosphate is cleaved to
glyceraldehyde & dihydroxy acetone
phosphate (DHAP) by aldolase B
• Glyceraldehyde is phosphorylated by
triokinase to glyceraldehyde 3-phosphate,
along with DHAP enters glycolysis or
gluconeogenesis.

23. Fructose entering glycolysis

24. Fructose
Sorbitol
Fru-1-P
Glyceraldehyde
Glycerol
Glucose
Fru-6-P
DHAP
NADP NADPH+H+
Reductase
NAD+
NADH+H+
DH
Glucose 6-P
Fru 1,6-BisP
Glycerol 3-P DHAP
Glyceraldehyde 3-P
PFK F-1,6 bis-P
Hexokinase
ATP
FructokinaseATP
Aldolase B
Triokinase ATP
Glycerol kinase
ATP
DH
Glycogen
NADH+H+
NAD

25. • It involves the conversion of glucose to
fructose via sorbitol
• Sorbitol pathway is higher in uncontrolled
diabetes
• The enzyme aldose reductase reduces glucose
to sorbitol in the presence of NADPH
• Sorbitol is then oxidized to fructose by Sorbitol
dehydrogenase and NAD+

26. Sorbitol pathway

27. • In uncontrolled diabetes, large amounts of
glucose enter the cells which are not
dependent on insulin
• The cells with increased intracellular glucose
levels in diabetes (lens, retina, nerve cells,
kidney etc) possess high activity of aldose
reductase and sufficient supply of NADPH.

28. • This results in a rapid & efficient conversion of
glucose to sorbitol
• The enzyme Sorbitol Dehydrogenase is either
low in activity or absent in these cells.
• Sorbitol is not converted to fructose.
• Sorbitol cannot freely pass through the cell
membrane and accumulate in the cells.

29. • Sorbitol-due to its hydrophilic nature-causes
osmotic effects leading to swelling of the cells.
• Pathological changes associated with
diabetes are due to accumulation of sorbitol.

30. • Essential fructosuria:
• Deficiency of the enzyme hepatic fructokinase.
• Fructose is not converted to fructose 1-
phosphate.
• Excretion of fructose in urine.
• Treatment: Restriction of dietary fructose
• Urine gives positive benedicts & seliwanoff’s
test

31. • An autosomal recessive inborn error.
• Due to defect in the enzyme aldolase-B.
• Fructose 1-phosphate, cannot be metabolised.
• Intracellular accumulation of fructose 1-
phosphate will inhibit glycogen
phosphorylase.
• Leads to accumulation of glycogen in liver &
associated with hypoglycemia

32. • Vomiting, loss of appetite, hepatomegaly &
jaundice.
• If liver damage progresses, death will occur.
• Fructose is excreted in urine.
• Restriction of dietary fructose.

33. • One or more hydroxyl groups of the
monosaccharides are replaced by amino groups
• E.g.D-glucosamine, D-galactosamine,
mannoseamine, sialic acid.
• They are present as constituents of GAG’s,
glycolipids & glycoproteins.
• Also found in some oligosaccharides &
antibiotics.

34. • The amino groups of amino sugars are
sometimes acetylated e.g.N-acetyl D-glucosamine
• Fructose 6-phosphate is major precursor for
glucosamine, N-acetylgalactosamine & NANA.
• N-Acetyl neuramic acid (NAN) is derivative of N-
Acetyl mannose & pyruvic acid.
• 20% of glucose is utilized for the synthesis of
amino sugars, which mostly occurs in the
connective tissues.

35. Glucose
Glu-6-P Fru-6-P Glucose
amine-6-P
Glucose
Amine-1-P
UDP-Glucose
Amine
N-Acetyl
Glucoseamine-6P
N-Acetyl
Glucoseamine1-P
GAGS
N-Acetylmannosamine-6-P
N-acetyl neuramic acid -9-P
UDP-N-
acetylglucosamine
UDP-N-
acetylgalactosamineCMP-NANA
Sialic acid
Gangliosides
Glycoproteins
GAGS
Glucosamine
PEP
Epimerase
Epimerase
UTP
CTP
UTP

36. References
• Textbook of Biochemistry-U Satyanarayana
• Textbook of Biochemistry-DM Vasudevan

37. Thank you