Fructose is metabolized primarily in the liver and small intestine. In the liver, fructose is converted to fructose-1-phosphate by fructokinase using ATP as energy. Fructose-1-phosphate is then cleaved by aldolase B into glyceraldehyde and dihydroxyacetone phosphate, which both enter glycolysis to generate energy. This pathway allows fructose to be rapidly metabolized and generates intermediates for glycolysis, though it requires two ATP per fructose molecule. Disorders of this pathway can cause hypoglycemia or liver failure if not treated by avoiding dietary fructose and sucrose.

1. Prepared by : Rabia Khan Baber

2. INTRODUCTION TO
FRUCTOSE METABOLISM
LOCATION OF FRUCTOSE
METABOLISM
PATHWAY OF FRUCTOSE
METABOLISM
SIGNIFICANCE OF
PATHWAY
FRUCTOSE METABOLISM
DISORDERS
REFERENCES

3.  Fructose is an abundant sugar in the human diet.
 This dietary monosaccharide is present naturally
in fruits and vegetables, either as free fructose or as part of
the disaccharide sucrose, and as its polymer inulin.
 Sucrose (table sugar) is a disaccharide which when
hydrolyzed yields fructose and glucose.
 The metabolism of fructose from dietary sources is referred
to as fructolysis.

4.  Under normal dietary intake the majority of the ingested
fructose is metabolized by the enterocytes of the small
intestine primarily to glucose which is then delivered to the
systemic circulation. In addition to glucose, the carbon
atoms from dietary fructose are converted, by intestinal
enterocytes, into several other metabolites including
glycerate, glutamate, glutamine, alanine, ornithine, and
citrulline.
 However, diets containing large amounts of sucrose, high
fructose corn syrup, or fructose alone, overwhelm the
ability of the small intestine to metabolize it all and under
these conditions a significant amount of fructose is then
metabolized by the liver and to a lesser extent by other
organs such as skeletal muscle.

5. SOURCES OF
FRUCTOSE
• The major natural
sources of fructose
in the human diet
are fruits, honey,
and sucrose.
LOCATION OF
FRUCTOSE
METABOLISM
• Fructose
metabolism takes
place primarily in
the cytoplasm of
cells of the liver.
SUBSTRATE
• Fructose (which is
derived from
breakdown of
sucrose in small
intestine).

6.  There are two pathways for the metabolism of fructose;
one occurs in muscle and adipose tissue, the other in
liver.
 In muscle and adipose tissue, fructose can be
phosphorylated by hexokinase (which is capable of
phosphorylating both glucose and fructose) to form
fructose 6-phosphate which then enters glycolysis.
 In liver, the cells contain mainly glucokinase instead of
hexokinase and this enzyme phosphorylates only
glucose. Thus in liver, fructose is metabolized instead
by the fructose 1-phosphate pathway:

8. FRUCTOSE
METABOLISM PATHWAY
Fructose is converted to
fructose 1-phosphate by
fructokinase with the use of
an ATP.
Fructose 1-phosphate is then
split into glyceraldehyde and
dihydroxyacetone phosphate
by fructose 1-phosphate
aldolase.
The dihydroxyacetone feeds
into glycolysis at the triose
phosphate isomerase step.
The glyceraldehyde is
phosphorylated by triose
kinase to glyceraldehyde 3-
phosphate using another ATP
and so also enters glycolysis.

9.  The aldolase family members involved in metabolism
and glycolysis are present in three
isoforms:ALDOA,ALDOB, andALDOC.Aldolases are
differentially expressed in human tissues,

10. ALDOLASE A- found in most tissues,
cleaves fructose1,6-bisphosphate to
DHAP and glyceraldehade 3- phosphate
ALDOLASE B- found in liver, only
aldolase B cleaves fructose 1-phosphate
ALDOLASE C- found in brain, cleaves
fructose1,6-bisphosphate to DHAP and
glyceraldehade 3- phosphate

11. RESULTS:
Generates 2
intermediate molecules
of glycolysis for each
molecule of fructose.
ENERGY
REQUIREMENT:
Requires 2 ATP.

12.  Allows fructose to be converted into intermediate
molecules in the glycolysis pathway.
 Since this pathway bypasses the rate-limiting step in
glycolysis, fructose is metabolized to pyruvate more
rapidly than glucose.

13. ESSENTIAL FRUCTOSURIA
 Essential fructosuria is a benign metabolic disorder
caused by the lack of fructokinase which is normally
present in the liver, pancreatic islets and kidney cortex.
The fructosuria of this disease depends on the time and
amount of fructose and sucrose intake. Since the
disorder is asymptomatic and harmless it may go
undiagnosed.

14. HEREDITARY FRUCTOSE INTOLERACNE
 Hereditary fructose intolerance (HFI) is a potentially
lethal autosomal recessive disorder resulting from a
lack of aldolase B which is normally expressed in the
liver, small intestine and kidney cortex. The incidence
of HFI is on the order of 1 in 20,000 live births. The
disorder is characterized by severe hypoglycemia and
vomiting following fructose intake. Prolonged intake of
fructose by infants with this defect leads to vomiting,
poor feeding, jaundice, hepatomegaly, hemorrhage and
eventually hepatic failure and death. Patients will
remain symptom free on a diet devoid of fructose and
sucrose.

15. FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY
 Hereditary fructose-1,6-bisphosphatase (F1,6BPase)
deficiency is a very rare autosomal recessive disease.
 Loss of fully functional FBP1 results in severely
impaired hepatic gluconeogenesis and leads to episodes
of hypoglycemia, apnea, hyperventilation, ketosis and
lactic acidosis. These symptoms can take on a lethal
course in neonates. Later in life episodes are triggered
by fasting and febrile infections.

16.  Textbook of Biochemistry-U Satyanarayana
 Textbook of Biochemistry-DM Vasudevan
 Smith, C. M., Marks, A. D., Lieberman, M. A., Marks,
D. B., & Marks, D. B. (2005). Marks’ basic medical
biochemistry: A clinical approach. Philadelphia:
Lippincott Williams & Wilkins.
 John W. Pelley, Edward F. Goljan (2011).
Biochemistry. Third edition. Philadelphia: USA.