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Fructose Metabolism
(Fructolysis)
Galactose metabolism
(Galactolysis)
Uronic acid pathway

Tewodros.shi
 Fructose Metabolism [ Fructolysis ]
Dietary sources :table sugar, honey and fruits
Absorption of fructose by = GLUT5
Ultimately it is converted into glucose and then glycogen or
directly into intermediates of glycolysis in the liver (kidney
and intestine to a smaller extent).
Fructose metabolism:
The predominance of liver , kidney & SI in the
metabolism of fructose is explained by the existence in
these tissues of a specialized pathway composed of 3
enzymes:
1- Fructokinase.
2-Aldolase B
3- Triokinase
Which convert fructose into intermediate of
glycolytic or gluconeogenic pathway
Fructose metabolism in liver

ATP Fat

Fructokinase - It is found in the liver, kidney, and

the small intestinal mucosa, and converts fructose to
fructose 1-phosphate, ATP as the phosphate donor.
Too Much Fructose
Fructose-1-P Aldolase is rate-limiting
Depletion of Pi
Reduction in [ATP]
Increase in glycolysis
Accumulation of lactate (acid) in blood

Increase fructose consumption may elevate plasma

TG & 1ry risk factor for atherosclerosis
Clinical correlations of Fructose Metabolism

Essential fructosuria is asymptomatic (rare or non-

disease) condition arising from deficiency of the enzyme
Fructokinase that causes a portion of fructose to be
excreted in the urine. or
Characterized by the presence of large amounts of
fructose in urine sufficient to give a positive reducing
sugar test ( normal administration 1-2% in urine but 10-
20% in FK deficiency )
Clinical correlations of Fructose Metabolism

Fructokinase
Fructose Fructose-1-p

Fructosuria
Aldolase-B

Hereditary Fructose Intolerance

D-Glyceraldehyde DHAP
 Hereditary fructose intolerance =HFI
No symptoms as long as the affected individual does
not ingest fructose.
Is due to Aldolase B deficiency
Symptoms appear upon introduction of cows milk
formulas sweetened with sucrose or at weaning when
fruits & vegetables are given
The inability to hydrolyze fructose 1-phosphate for
further metabolism.
==Accumulation of it in liver and kidney !!!
Reduces availability of Inorganic phosphate and
decreases ATP levels. (Sequestration).
Treatment: In hereditary fructose intolerance, sucrose as well as
fructose, must be removed from the diet to prevent liver failure and
possible death.
Insufficient inorganic phosphate (especially in the liver
cells of affected persons who ingest a large amount of fructose)
impairs gluconeogenesis, protein synthesis,RNA,DNA and
energy production by oxidative phosphorylation and NH3
detoxification in Urea cycle .
The inhibition of gluconeogenesis results in lactic
acidosis

Because GTP & Pi are inhibitors of liver AMP

deaminase , their depletion provokes degradation of
hepatic adenine nucleotide & increased production of uric
acid.
Symptoms: Vomiting, severe hypoglycemia, liver disease
 Galactose Metabolism
Dietary source is lactose from milk and milk products.
The digestion of lactose by lactase
Metabolized by phosphorylation to galactose1-phosphate, and

then conversion to UDP-galactose and glucose 1-phosphate.

The enzyme involve :

Galactokinase,
Galactose l-phosphate Uridyltransferase.
UDP-glucose epimerase.
 Enzymes required for galactose metabolism
Gala. Kinase
1st Galactose Galactose 1-P

ATP ADP UDP-Glu

Uridyl transferase Epimerase

2nd 3rd

UDP-Gal
Glucose 1-P
Mutase
Glucose 6-P
Glycolysis
 Clinical correlation of galactose metabolism

In classical Galactosemia, a deficiency of Galactose 1-phosphate

uridylyltransferase.
Galactose 1-phosphate accumulates, and excess galactose is converted to
galactitol by aldose reductase. This causes liver damage, severe mental
retardation, and cataracts.
In nonclassical Galactosemia, a deficiency of Galactokinase results in
the accumulation of galactose in blood and urine.
Treatment : avoid lactose rich food
 URONIC ACID PATHWAY
Uronic acid pathway is another minor alternative
pathway for glucose oxidation by which:
Glucuronic Acid,
Ascorbic Acid And
Pentoses Are synthesized.
It is neither requires nor generates ATP.

Site: It occurs in Cytosol of many tissues, especially

liver, kidney and intestine.
 Glucose-6-P
Phosphoglucomutase

Glucose-1-P
UDP Glucose UTP
pyrophosphorylase PPi 2Pi
UDP-Glucose
H2O NAD(P)+
UDPG Dehydrogenase
NAD(P)H
Conjugation Reactions
Proteoglycans UDP-Glucuronic Acid to Synthesise
H2O Glucuronides
Hydrolase
1st Glucuronic Acid
UDP

NADPH
NADP+ NAD+
L-Gulonic Acid NADH

L-Gulonic Acid 3-Keto-L-Gulonic Acid

CO2 CO2
L-Gulonolactone L-Xylulose
O2 NADPH
Block in Primates & Guinea Block in Essential Xylitol DH
Pigs Pentosurina NADP+

2-Keto-L-Gulonolactone Xylitol
NAD+
Xylitol DH

3rd
NADH
D-Xylulose
L-Ascorbic Acid 2nd
Note: Many animals can Synthesize Ascorbic acid from
glucose.
=Man, other primates guinea pigs and bats Cannot
synthesize ascorbic acid due to the Deficiency of L-
Gulconolactone Oxidase.
 Biological Importance of Uronic Acid Pathway
The pathway is an alternative pathway for synthesis of pentoses along
with the pentose pathway.
It is also a source for vitamin C synthesized in plants and mammals
except human, primates and guinea pigs.

Synthesis of UDP-glucuronic acid participates in the following

reactions:
Synthesis of mucopolysaccharides
Detoxication of xenobiotics (drugs and toxins) by
conjugation in the liver.
This enhances drug clearance by glucuronate-drug
conjugation and leads to drug resistance.
Excretion of endogenous metabolites, e.g., steroid
hormones and bilirubin by conjugation.
iClicker Quiz
Q:Enzymes is not directly required in the
sequence of reactions by which galactose is converted
to UDP-glucose?
1. Galactokinase
2. An epimerase
3. Phosphoglucomutase
4. Uridyl transferase
Q: Caused by a deficiency in Aldolase B
patients with this have hypoglycemia because elevated
F1P inhibits glycogen phosphorylase thus inhibiting
glycogenolysis; also because gluconeogenesis is inhibited
because aldose B is required for glucose synthesis from
glyceraldehyde-3-P and DHAP

ANSWER: hereditary fructose intolerance

Q: Deficiency in Galactosemia; causes hypergalactosemia
and cataracts

ANSWER: nonclassical Galactosemia

Q: Caused by a deficiency in Fructokinase; rare and benign
genetic disorder because no toxic metabolites of fructose
accumulates in the liver
1.Nonclassical Galactosemia
2.Essential fructosuria
3.Polyol pathway
4.Classical Galactosemia

Why vitamin c is not synthesized by the human being and

ginea pig ?????????
10 Q 4 Ur Kind Attention!!