Carbohydrates metabolism

2. ‫اآلية‬ ‫البقرة‬ ‫سورة‬
32

3. Department of Biochemistry
Faculty of Pharmacy
Damanhour University
CARBOHYDRATE
METABOLISM

4. 17
Fates of the body sugars
 In the liver fructose and mannose are changed to
glucose. Glucose may undergo one of many fates, as
follows:
1- Oxidative fate:
- Major pathways: Glycolysis and Krebs' cycle.
- Minor pathways: Pentose shunt and Uronic acid pathway.
2- Anabolic fates:
- Glycogenesis/glycogenolysis. - Gluconeogenesis.
- Monosaccharides synthesis. - Lactose synthesis.
- Glycolipids, glycoproteins and Proteoglycans synthesis.
CARBOHYDRATE METABOLIISM

5. 18
Glycolysis
Definition:
 It is a cascade of reactions that converts glucose
into two pyruvate molecules (when O2 is available)
or into lactate (when O2 is not available, i.e., no
mitochondria) aiming at production of ATP and
other intermediates. It is also utilized in its opposite
direction in gluconeogenesis
CARBOHYDRATE METABOLIISM

6. 19
 Intracellular site and tissue distribution:
 It occurs in the cell cytoplasm of all tissues of the
body. It is especially important in:
1- RBCs are devoid of mitochondria.
2- Cornea, lens and some parts of retina
3- Kidney (medulla), testicles, leukocytes and white muscle
4- Contracting muscles due to occlusion of blood vessels.
5- Cancer cells.
6- Brain and gastrointestinal tract.
CARBOHYDRATE METABOLIISM

7. CHO
OH
H
H
HO
OH
H
OH
H
CH2OH
CHO
OH
H
H
HO
OH
H
OH
H
CH2-O P-OH
OH
O
ATP
Mg+2
CH2OH
O
H
HO
OH
H
OH
H
CH2-O P-OH
OH
O
ATP
Mg+2
CH2-O
O
H
HO
OH
H
OH
H
CH2-O P-OH
O
P-OH
OH
O
ADP
CHO
OH
H
CH2-O P-OH
OH
O
CH2-O
O
CH2OH
P-OH
OH
O
2 NAD + Pi
2 NADH.H+
OH
H
CH2-O P-OH
OH
O
P-OH
OH
O
C ~
O
C
OH
H
CH2-O P-OH
OH
O
O
Mg+2
OH C
O
H
CH2-OH
O
OH
P-OH
OH
O
2 H2O
Mg+2
C
O ~
CH2
O
OH
P-OH
OH
O
Mg+2
C
OH
CH2
O
OH
C
O
CH3
O
OH
C
OH
CH3
O
OH
H
ADP+Pi
Glucose
Glucose-6-Phosphate Fructose-6-Phosphate
Phosphohexose
Isomerase
Phosphofructokinase
Fructose-1,6-
diphosphate
(2) Glyceraldehyde-
3-phosphate
Dihydroxyacetone-
phosphate
Phosphotriose
Isomerase
Aldolase
A or B
(2) 1,3-DiPhospho-
Glycerate
Glyceraldehyde-
3-Phosphate
Dehydrogenase
(2)
2 ADP
Phosphoglycerate
Kinase
2 ATP
3-Phospho-Glycerate
(2) 2-Phospho-Glycerate
Enolase
(2) Phosphoenol
Pyruvate
3-Phospho-
Glycerate
Mutase
2 ADP
Pyruvate
Kinase
2 ATP
(2) Enol-
Pyruvate
(2) Pyruvate
2 NAD
Lactate
Dehydrogenase
2 NADH.H+
(2) Lactate
Spontaneous
Hexokinase, or
Glucokinase
OH

9. 21
1. Phosphorylation of glucose
 The irreversible phosphorylation reaction effectively
traps glucose as glucose 6-phosphate, which does
not diffuse out of the cell.
 Phosphorylated sugar molecules do not readily
penetrate cell membranes because there are no
specific carriers for these compounds.
CARBOHYDRATE METABOLIISM

10. 22
i) Hexokinase:
 In most tissues the phosphorylation of glucose is
catalyzed by hexokinase, one of three regulatory
enzymes of glycolysis
a. Substrate specificity and product inhibition:
Hexokinase has a broad specificity and is able to
phosphorylate several hexoses in addition to
glucose.
b. Hexokinase is inhibited by the reaction product,
glucose 6-phosphate and high ATP/ADP ratio.
CARBOHYDRATE METABOLIISM

11. b. Kinetic properties:
 Hexokinase has a low Km (and therefore a high
affinity for glucose).
 Hexokinase, however, has a low Vmax for glucose
and therefore cannot phosphorylate large quantities
of glucose.
ii) Glucokinase: In liver, glucokinase is the predominant
enzyme for the phosphorylation of glucose.
 Km, Vmax, substrate inhibition ????????????
23
CARBOHYDRATE METABOLIISM

12. 2- Isomerization of glucose 6-phosphate
The isomerization of glucose 6-phosphate (an aldose
sugar) to fructose 6-phosphate (a ketose sugar) is
catalyzed by phosphoglucose isomerase.

13. 3- Phosphorylation of fructose 6-phosphate
 The irreversible phosphorylation reaction catalyzed by
{PFK-1) is the most important control point of glycolysis.
 The PFK-1 reaction is the rate-limiting step in glycolysis.
 PFK-1 is controlled by the concentrations of the
substrates ATP and fructose 6-phosphate, and by
regulatory substances.
ATP
Mg+2
Phosphofructokinase
CH2OH
O
H
HO
OH
H
OH
H
CH2-O P-OH
OH
O
Fructose-6-Phosphate
CH2-O
O
H
HO
OH
H
OH
H
CH2-O P-OH
OH
O
Fructose-1,6-diphosphate
P-OH
OH
O
ADP

14. 4- Cleavage of fructose 1,6-bisphosphate.
5- Isomerization of dihydroxyacetone phosphate.
6- Oxidation of glyceraldehyde 3-phosphate
 The conversion of glyceraldehyde 3-phosphate to 1,3-
bisphosphoglycerate by glyceraldehyde 3-phosphate
dehydrogenase is the first oxidation-reduction reaction

15.  Because there is only a limited amount of NAD+ In the
cell, the NADH formed must be reoxidized to NAD+ for
glycolysis to continue.
 Two major mechanisms for oxidizing NADH are
(1) The NADH-linked conversion of pyruvate to lactate.
(2) oxidation via the respiratory chain.
 The oxidation of the aldehyde group of glyceraldehyde 3-
phosphate to a carboxyl group is coupled to the
attachment of Pi to the carboxyl group.

16.  The high energy phosphate group at carbon 1 of 1,3-
bisphosphoglycerate conserves much of the free energy
produced by the oxidation of glyceraldehyde 3-
phosphate.
 The formation of 1,3-bisphosphoglycerate is an example
of substrate level phosphorylation in which the production
of a high-energy phosphate is coupled directly to the
oxidation of a substrate, instead of resulting from
oxidative phosphorylation via the electron transport chain
 The energy of this high-energy phosphate drives the
synthesis of ATP in the next reaction of glycolysis.