biochemistery

2. METABOLISM OFMETABOLISM OF
GALACTOSEGALACTOSE

3. Introduction
Galactose forms a small part of carbohydrate intake,
being present in the diet only in the form of the
disaccharide lactose found in milk.
Galactose is an important component of lactose,
glycoproteins, and glycolipids.
The uptake of galactose by cells is insulin
independent; and galactose does not stimulate
insulin secretion.

4. Galactose
ATP
Mg2+
ADP
Galactokinase
Galactose-1-phosphate
Gal-1-P-Uridyl transferase
Glucose-1-phosphate
Phosphoglucomutase
Glucose-6-P
H2O
G-6-Pase
Pi
Glucose
Utilization in the liver
UDP-Glu
UDP-Gal
UDP-Gal-4-epimerase
Conversion of galactose to glucose

5. Conversion of galactose to glucose is the only way to catabolize
galactose. It is a slow process that occurs only in the liver. The ability
of the liver to convert galactose to glucose may be used as a liver
function test.
Galactose is converted to galactose 1-phosphate in a reaction
catalyzed by galactokinase, with ATP as phosphate donor.
Galactose 1-P replaces glucose 1-phosphate from UDP-glucose,
forming UDP-galactose. The reaction is catalyzed by galactose I-
phosphate uridyl transferase. The liberated glucose 1-phosphate may
be utilized for glycogenesis or converted by phosphoglucomutase to
glucose 6-phosphate. The latter may undergo glycolysis or becomes
converted to glucose by glucose 6-phosphatase.
UDP-galactose is converted to UDP-glucose in a reaction catalyzed by
UDPgalactose 4-epimerase. Thus, UDP-glucose is considered as a
coenzyme in the conversion of galactose to glucose.

6. UDP-Glu
Glucose
Glucokinase
Hexokinase
Glucose-6-P
ATP
Mg2+
ADP
Lactose
UDP Glucose
Lactose synthase
UDP-Gal
Glycolipids and glycoproteins
Phosphoglucomutase
Glucose-1-P
UDP-Glu
pyrophosphorylase
UDP-Gal-4-epimerase
UTP
PPi
Lactose synthesisLactose synthesis

7. Galactosemia
Galactosemia is an inherited disease usually caused
by deficiency of galactose 1-phosphate uridyl
transferase, and rarely galactokinase or UDP-
galactose 4-epimerase.
Galactosemia and galactosuria occur after the intake
of galactose or lactose. It causes cataract in infancy,
principally due to the conversion of galactose to its
alcohol galactitol (dulcitol) by the enzyme aldose
reductase. Galactitol cannot leave the eye lens,
leading to the accumulation of excess water and
osmotic damage.
Deficiency of the enzyme galactose 1-phosphate
uridyltransferase leads to mental deficiency and
hepatomegaly. In addition, attacks of hypoglycemia
may follow the intake of lactose. This is probably due
to the accumulation of galactose 1-phosphate,
leading to sequestration of phosphate needed for
glycogenolysis.
Galactosemia can be treated by giving artificial milk
that does not contain lactose (e.g. Beblac FL).

8. METABOLISM OFMETABOLISM OF
FRUCTOSEFRUCTOSE

9. Introduction
Fructose forms about 20% of our carbohydrate intake. It is
found in sucrose (table sugar and molasses), honey, and some
fruits.
The uptake of fructose by cells is insulin independent; and
fructose does not stimulate insulin secretion.
Fructose absorption is not dependent on sodium gradient. It is
transported into the intestinal cells by a facilitated diffusion by
GLUT5. Fructose transport is less rapid than glucose transport.
Fructose enters the blood stream, along with glucose and
galactose via the GLUT2 transporter.
Fructose is taken up by the liver by GLUT2 transporter.
Fructose uptake by hepatocyte is low

10. Utilization of fructose
1- In liver: Fructose is converted to glucose. It is metabolized
mainly in the liver by the fructokinase enzyme to form F-1-P.
then by the action of fructose-1-phosphate aldolase (aldolase
B), F-1-P is converted to DHAP and glyceraldehyde. The latter
is converted to glyceraldehyde-3-phosphate by the thiokinase.
DHAP and glyceraldehyde-3-phosphate form glucose by
reversal of glycolysis or converted to pyruvate by glycolysis.
The utilization of fructose by fructokinase then aldolase B, bypass
the steps of glucokinase and PFK1 which are activated by insulin.
This explains why fructose disappears from blood more rapidly
than glucose in diabetic subjects.

11. glucose
Fructose
Fructokinase
Fructose 1- P
Aldolase B
Glyceraldehyde
Mg2+
ATP ADP
DHAP
Fructose 6-P
Fructose 1,6-
bisphosphatase
Fructose 1,6-
bisphosphate
Aldolase
Glyceraldehyde 3-P
Hexose phosphate
isomerase
H2O Pi
Glucose 6-P
Glucose 6- phosphatase
ThiokinaseMg2+
ATP
ADP

12. Conversion of glucose to fructose
Fructose is the preferred fuel for sperms. In the seminal
vesicles, glucose is converted to fructose, which is secreted in
semen, via the sorbitol pathway. Glucose is first reduced to
sorbitol in a reaction catalyzed by the enzyme aldose
reductase. sorbitol undergoes dehydrogenation, forming
fructose, in a reaction catalyzed by the enzyme sorbitol
dehydrogenase.
Aldose reductase
D-Glucose
NADPH + H+
NADP+
D-Sorbitol
Sorbitol dehydrogenase
D-Fructose
H-C=O
I
H-C-OH
I
R
CH2-OH
I
C=O
I
R
CH2-OH
I
H-C-OH
I
R NADPH + H+
NADP+

13. Aldose reductase is present in the eye lens, retina, nervous
tissue, and renal glomeruli, and placenta, but not in the liver.
On the other hand, sorbitol dehydrogenase is virtually absent
from these tissues, but present in the liver.
The activity of aldose reductase markedly increases in diabetes
mellitus due to increased glucose levels, leading to increased
concentrations of sorbitol (does not diffuse through cell
membranes easily) in these tissues. This causes osmotic
damage, which explains cataract, retinopathy, neuropathy,
nephropathy, and placental damage in cases of untreated
diabetes mellitus. These complications of diabetes can be
prevented by the use of aldose reductase inhibitors.

14. Hereditary defects in fructose
metabolism
These metabolic inborn errors include mainly:
Essential fructosuria : It is a rare benign genetic disease
due to deficiency of the fructokinase enzyme and
manifested by fructosemia and fructosuria.
Hereditary fructose intolerance: It is due to hereditary
deficiency of the liver enzyme aldolase B. This leads to
accumulation of fructose-1-phosphate and depletion of liver
ATP and phosphate stores, which produces inhibition of
glycogen phosphorylase and hypoglycemia after fructose
feeding.