CARBOHYDRATE

METABOLISM
METABOLISM
 Carbohydrate Metabolism/
Utilization- Tissue Specificity
• Muscle – cardiac and skeletal
– Oxidize glucose/produce and store glycogen (fed)
– Breakdown glycogen (fasted state)
– Shift to other fuels in fasting state (fatty acids)
• Adipose and liver
– Glucose → acetyl CoA
– Glucose to glycerol for triglyceride synthesis
– Liver releases glucose for other tissues
• Nervous system
– Always use glucose except during extreme
fasts
• Reproductive tract/mammary
– Glucose required by fetus
– Lactose → major milk carbohydrate
• Red blood cells
– No mitochondria
– Oxidize glucose to lactate
– Lactate returned to liver for
Gluconeogenesis
Carbohydrate metabolism includes

1. Digestion of carbohydrates.
2. Absorption of digested carbohydrates.
3. Utilization of carbohydrates
 Major Pathways of CHO
Metabolism
CHO metabolism in mammalian
cells can be classified into:
1. Glycolysis: Oxidation of
glucose to pyruvate (aerobic
state) or lactate (anaerobic
state)
2. Krebs cycle: After oxidation
of pyruvate to acetyl CoA,
acetyl CoA enters the Krebs
cycle for the aim of production
of ATP.
3. Hexose monophosphate shunt: Enables cells
to produce ribose-5-phosphate and NADPH.
4. Glycogenesis: Synthesis of glycogen from
glucose, when glucose levels are high
6. Glycogenolysis: Degradation of glycogen to
glucose when glucose in short supply.
7.Gluconeogenesis: Formation of glucose from
noncarbohydrate sources.
 Utilization
A-Anabolic pathways:
Transforming small molecules into big molecules
constituting the body structures and machinery. It is energy
requiring, e.g., glycogenesis and lactose synthesis

B-Catabolic pathways:
Breakdown of large molecules into smaller molecules
to produce energy or smaller molecules or reducing
equivalents, e.g., HMP-shunt and uronic acid pathway.

C-Amphibolic pathways:
They are utilized for both anabolic and catabolic
purposes, e.g., glycolysis and Krebs' cycle.
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Digestible carbohydrates:
starch, glycogen, maltose, sucrose, and lactose
(oligosaccharides and polysaccharides).

Ready-to-absorb carbohydrates:
Which do not need digestion and are absorbed as such,
e.g., monosaccharides: glucose, mannose, galactose,
fructose and pentoses.

Non-digestible carbohydrates:
Which are called dietary fibers.
These include cellulose, gums and pectins.
They are very important for stools excretion and are
anticancer and intestinal bacteria feed on it to release
certain vitamins.
 Carbohydrate Digestion in the buccal cavity:
• In the mouth, salivary amylase is produced
by the salivary glands.
• Its optimum pH is 6.7 - 6.8 and is activated
by chloride ions.
• It is a -glycosidase specific for hydrolysis of
-1,4 glucosidic linkage present in cooked
starch and glycogen producing maltose and
dextrins.
• Salivary amylase cannot digest -1,4-
glucosidic linkage in cellulose.
 2. Carbohydrate digestion in the
Stomach:

Salivary amylase continues to act on

starch, glycogen or dextrins for 2 - 3
minutes only in the stomach (acidic pH
1 - 2).
 3. Carbohydrate digestion in the Small
Intestine:

In the small intestine, there are two

juices that digest carbohydrates:
A. The pancreatic juice:
This juice contains pancreatic amylase,
an -glycosidase. It has an optimum
pH 7.1 and is also activated by chloride
ion.
 B. Intestinal mucosal brush border enzymes:

The final digestion of carbohydrates

occurs in the small intestine by the
action of the following
disaccharidase:
Lactase hydrolyzes lactose into glucose
and galactose.
 Dietary fibers
1. The -1,4 glucosidic linkage of Cellulose is not
hydrolyzed by human digestive enzymes.
2. Hemicellulose, gums, pectins and pentosans are
also indigestible.
3. Cellulose and other dietary fibers passes as it is in
stools, increasing bulk of intestinal contents by
adsorbing water and stimulates peristaltic
movements to reduces stool transit time and
prevents constipation.
4. They bind and dilute bile acids.
5. The more soluble fibers found in legumes and
fruit, e.g., gums and pectins, lower blood
cholesterol, possibly by binding bile acids and
dietary cholesterol.
6. The soluble fibers also slow the stomach
emptying and attenuate the post-prandial
rise in blood glucose that spares insulin.
7. This effect is beneficial to diabetics and to
dieters because it reduces the rebound
fall in blood glucose that stimulates
appetite
8. It induces establishment of normal colon
bacteria with several benefits including
fermentation of fibers and production of
vitamins (e.g., vit. K)
 Site of absorption:

• Mainly the upper part of small intestine,

i.e., jejunum.
• Very small amount is absorbed in the
stomach or large intestine.
 Route of absorption

By the portal vein to the liver, i.e., blood

stream chiefly in the form of hexoses
(glucose, fructose, mannose and
galactose) and as pentose sugars (ribose).
 Mechanism of absorption (or
transport):
A) Facilitated absorption:
This mechanism is the most active for
fructose and pentoses but is utilizable
by glucose and galactose if their
lumenal concentration is favorable.
 B) Active absorption:
• This absorption occurs against
concentration gradient, i.e., sugars
are absorbed from low to high
concentration and requires the
presence of an OH group on C2 at
the right side of a pyranose ring and
a methyl group or a substituted
methyl group at C5.
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 Fate of glucose
A-Oxidative fate:
• Major pathways: A. Glycolysis. B. Krebs' cycle.
• Minor pathways: A. Pentose shunt. B. Uronic acid
pathway.

B- Anabolic fates:
• Glycogenesis/glycogenolysis.
• Gluconeogenesis.
• Monosaccharides synthesis.
• Lactose synthesis.
• Glycolipids, glycoproteins and Proteoglycans
synthesis.
 Major Oxidative Pathways of
Glucose:

Glycolysis
Embden-Myerhof Pathway
Anaerobic Oxidation of Glucose
 Definition:

• It is a cascade of reactions that converts

glucose into two pyruvate molecules or
into lactate aiming at production of ATP
and other intermediates.
• It is also utilized in its opposite direction in
gluconeogenesis.
 Intracellular site and tissue
distribution:
It occurs in the cell cytosol of all tissues of the body.

1.RBCs:
are devoid of mitochondria and depend on glycolysis as the main source
of energy. Mammalian erythrocyte is unique in that about 90% of its
total energy requirement is provided by glycolysis.

2.Contracting muscles
due to occlusion of blood vessels by the muscular contraction that
decreases oxygen

3-Cornea, lens and some parts of retina

which have a limited blood supply and lack mitochondria which if
present would absorb and scatter light interfering with transparency.
4-Kidney (medulla), testicles, leukocytes and white
muscle fibers,
where there are relatively few mitochondria.

5-Cancer cells
due to dissociation of the high rate of glycolysis from
Krebs', i.e., aerobic production of lactate.

6-Brain and gastrointestinal tract also normally derive

most of their energy from glycolysis.
 Biological importance (or
Functions) of glycolysis:
1. Glucose oxidation producing ATP.
2. It is the major source of energy in certain tissues,
e.g., RBCs and skeletal muscles.
3. It provides pyruvic acid needed for Krebs' cycle.
4. It is a link with fat metabolism, e.g.,
dihydroxyacetone phosphate into glycerol 3-
phosphate in adipose tissue.
5. It a link with amino acid metabolism, e.g., 3-
phopshoglycerate into serine and pyruvate into
alanine and vice versa.
6. Production of 2,3-DPG that is important in tissue
oxygenation.
7. It is the major source of lactic acid that is
gluconeogenic.
8. Reversal of glycolysis is gluconeogenesis, an
important source of glucose.
9. Main pathway of metabolism of fructose from the
diet.
10. A small number of genetic diseases occur due to
deficiency in activity of enzymes of glycolysis, are
manifested mainly as hemolytic anemias.
11. Cancer cells are glycolytic producing large amount
of lactate, favoring a relatively acidic local pH in
the tumor, a situation that was utilized to develop
therapy for cancer that could be locally activated
by this acidic pH.
Steps of glycolysis
Bioenergetics of (or Energy
yield from) glycolysis:
Under anaerobic conditions:
1- Total ATP lost = 2 ATP as follows,
One ATP in the activation of glucose to glucose-6-
phosphate.
One ATP in the activation of fructose-6-phosphate to
fructose1,6-diphosphate.

2- Total ATP gained = 4 ATP as follows,

2 ATP by substrate level phosphorylation from 1,3-
diphosphoglycerate
2 ATP from substrate level phosphorylation from
phosphoenol pyruvate.
3- Net ATP gained = 4 ATP gained - 2 ATP lost = 2 ATP
for the anaerobic oxidation of one mole of glucose into
lactate.
Under aerobic conditions:
Total ATP lost = 2 ATP.
Total ATP gained = 10 ATP are generated as
follows,
4 ATP (obtained by substrate level
phosphorylation) + 2 NADH.H+ chain
(produced from oxidation of glyceraldehyde-3-
phosphate)  2 X 3 ATP = 6 ATP, after
oxidation in the functioning respiratory
Net ATP gained = 8 ATP as follows,
10 ATP – 2 ATP = 8 ATP for the aerobic
oxidation of one mole of glucose.
Regulation (or Control) of
Glycolysis
A. Key regulatory enzymes:
are those enzymes that catalyze the
irreversible steps of glycolysis that
include three steps as follows,

1-Phosphofructokinase:
It is an allosteric enzyme stimulated by
high levels of fructose-6- phosphate,
fructose-2,6-diphosphate (in liver), ADP
and AMP, Pi, and ammonia.
It is inhibited allosterically by ATP, low pH
and citrate.
2-Hexokinase:
Accumulation of glucose-6-phosphate and
inhibition of phosphofructokinase results in
accumulation of fructose-6-phosphate and
glucose-6-phosphate that allosterically inhibit
hexokinase.
3-Pyruvate kinase: It is inhibited also by
excess ATP, fatty acids, and acetyl-CoA
and is stimulated by fructose-1,6-diphosphate,
ADP and AMP
It is regulated by cAMP-dependent
phosphorylation-dephosphorylation
mechanism
B. Hormonal regulation:
1. Insulin:
Stimulates synthesis of glucokinase,
phosphofructokinase and pyruvate kinase,
so it stimulates glycolysis.
It also induces glucose transporters to
provide cells with glucose for glycolysis.

2-Adrenaline and glucagon are

inhibitory by inhibiting pyruvate kinase.
 Hexokinase Glucokinase

Km High (10mM) Low (<0.1mM)

Affinity Low affinity High affinity

Vmax High Low

Tissue Liver, pancreas muscle and other

distribution tissues
glu6PO4 Inhibited Is not inhibited

Insulin Is not regulated by regulated by insulin

insulin
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