Bio l4,5

Dr. Hani Alrefai
04/11/2014
Dr. Hani Alrefai 04/11/2014

 How is carbohydrate digested and absorbed
in our body.
 Metabolism of Glycogen in the body
 Glycogen metabolism diseases.
 Difference between glycogen in the liver and
in the muscle.

1- Passive diffusion (Simple
absorption): The absorption
depends upon the
concentration gradient of
sugar between intestinal
lumen and intestinal
mucosa. This is true for
pentoses and fructose.
2- Facilitative diffusion: by
Na+-independent glucose
transporter system (GLUT
5). There are a mobile
carrier protein responsible
for transport fructose,
glucose, and galactose with
their conc. gradient.

3- Active transport: by sodium-
dependent glucose transporter
system (SGLUT 1). In the
intestinal cell membrane there is
a mobile carrier protein coupled
with Na+-K+ pump. The carrier
protein has 2 separate sites one
for Na+ & the other for glucose.
It transports Na--+ ions (with
cone. gradient) and glucose
(against its cone. gradient) to
the cytoplasm of the cell . Na+
ions is expelled outside the cell
by Na+-K+ pump which needs ATP
and expel 3 Na+ against 2 K+.

 Glucose is transported through cell membrane of
different tissues by different protein carriers or
transporters as follows :
1- GLUT 1 : present mainly in red blood cells.
2- GLUT 2 : present in liver, kidneys, pancreatic B
cells and lateral border of small intestine, for
rapid uptake and release of glucose.
3- GLUT 3 : present mainly in brain.
4- GLUT 4 : present in muscles (Skeletal and
cardiac) and adipose tissues. (Insulin)
5- GLUT 5 : present in small intestine for sugar
absorption.
6- SGLUT 1 : present in small intestine and
kidneys.

 Def.: it is the formation of glycogen from
glucose in muscles and from CHO and non
CHO substances in liver.
 Site and location: In the cytoplasm of every
cell mainly liver and muscles.
 Steps:

 Steps:
3. Glycogen synthase enzyme in
presence of pre-existing glycogen
primer (glycogenin) will add
glucose mol. from UDP-G by
forming l :4 glucosidic link.
4. When the chain has been
lengthened, the branching
enzyme (glucan transeferas)
transfers a part of the a 1:4 chain
to a neighbouring chain to form
an l:6 glucosidic link. Thus
establishing the branching points
in the molecule. The branches
grow by further addition of 1:4
glucosyl units.

 Def.:
It is the breakdown of glycogen into glucose in liver and lactic
acid in muscles.
 Steps:
1. Phosphorylase enzymes attacks only a 1:4 glucosidic link at
the end of the chain until there are 4 molecules of glucose
near the branching point giving G-l-P in presence of Pi.
2. Transferase enzyme transfers trisaccharides unite (from this
4 mol.) from one branch to another exposing a l: 6 branching
point.
3. The branching point is splitted by debranching enzyme giving
free glucose.
4. G-l-P is changed to G-6-P by the action of phosphoglucose
mutase enzyme.
5. G-6-P is hydrolysed into free glucose and Pi by the action of
G-6-phosphatase -> free glucose diffuse from liver cell to
blood stream. In muscles there is no G-6-phosphatase -> so G-
6-P by glycolysis will give lactic acid.

 The key regulatory enzyme of glycogenesis is
glycogen synthase which present in 2 forms:
- Active form which is dephosphorylated enzyme.
- Inactive form which is phosphorylated enzyme.
 The key regulatory enzyme of glycogenolysis is
phosphorylase enzymes which present 2
forms.
-Active form which is phospho -phosphorylase enzymes.
-Inactive form which is Dephospho-phosphorylase .

Epinephrine stimulates α adrenergic
receptor
→ activate PLC → hydrolyse PIP2→ IP3 → Ca+
from endoplasmic reticulum → Ca+ reacts
with calmoduline to give Ca+-calmoduline
complex → stimulate PKC (protein kinase C)
phosphorylation of :
→glycogen synthase (inactive form)
→ phosphorylase(active form)
→ → → → → stimulate glycogenolysis and
inhibit glycogenesis.

Epinephrine stimulates β adrenergic
receptors and Glucagon stimulates its
receptors
→ stimulate adenylate cyclase enzyme →
cyclic AMP formation → stimulate protein
kinas A phosphorylation of:
→glycogen synthase (inactive form)
→ phosphorylase(active form)
→ → → → → stimulate glycogenolysis and
inhibit glycogenesis.

 Insulin
Stimulate phosphatase enzyme dephosphorylation of :
→glycogen synthase (active form)
→ phosphorylase(inactive form)
→ → → → → inhibit glycogenolysis and
stimulate glycogenesis.
Also stimulate phosphodiesterase enzyme → destruct
cyclic AMP.

Liver glycogen Muscle glycogen
- Amount Liver has more conc. muscle has more amounts.
- Sources blood glucose and other
radicals
blood glucose only
- Hydrolysis give blood glucose due to absence of
phosphatase enzyme not
give free glucose but give
lactic acid
- Starvation changes to blood glucose not affected.
- Muscular ex. depleted. depleted.
- Hormones  insulin → ↑↑↑
 adrenaline →↓↓↓
 thyroxine →↓↓↓
 glucagons →↓↓↓
 insulin → ↑↑↑
 adrenaline → ↓↓↓
 Thyroxine → ↓↓↓
 glucagons → no
effect due to absence of its
receptors

 A group of diseases results from genetic
defects of certain enzymes.
1. Von Gierke (type I) hepatorenal glycogen
storage disease: glucose-6-phosphatase
enzyme
2. Pompe's (lysosomal glucosidase deficiency).
3. Forbe's (Debranching enzyme efficiency).
4. Andersen's (Branching enzyme system
deficiency).
5. McArdle's (Muscle phosphorylase
deficiency).
6. Hers's (Liver phosphorylase deficiency).
7. Taui's (Phosphofuctokinase deficiency).

Dr. Hani Alrefai
11/11/2014

 Regulation of Glycolysis
 Carbon sources of gluconeogenesis
 Cori cycle
 Krebs cycle
 Energy production of glucose oxidation

 Def.:
glycolysis is oxidation of glucose to give pyruvic
acid in presence of O2 and lactic acid in absence
of O2 and in RBCs.
 Site:
Cytoplasm of all cells.

Glucokinase/

G → G-6-P -1
F-6-P → F l:6diphosphate -1
(1,3 DPG → 3-phosphoglycerate)X2 +2
(Phosphoenol pyruvate → pyruvate)X2 +2
Net ATP/mol glucose (anerobic) 2
2NADH+H from Glyceraldhyde3PD +4 or 6
Net ATP/mol glucose (aerobic) 6 or 8
If we started in the muscle from glycogen we start
from G-6-P so we have 1 extra ATP

Enzymatic:
 Hexokinase
 Glucokinase
 PFK
 PK
Hormonal:
 Glucagon
 cAMP
 Represion of Key
reg. enzymes
 Insulin
 Phosphatase
 cAMP
 Induction of Key
reg. enzymes
Regulations:

1. Iodoacetate:
inhibits glyceraldehyde-3-P dehydrogenase
2. Fluoride:
inhibits enolase

Aerobic
glycolysis
Anaerobic
glycolysis
Site Cytoplasm of all
tissues
RBCs and
skeletal muscle
during muscular
ex.
End products Pyruvic acid +
NADH.H+
Lactic acid +
NAD+
Energy
production
6 OR, 8 ATP 2 ATP
Lactate
dehdyrogenase
Not needed Needed

 Def.:
It is the formation of glucose form non CHO sources.
 Function :
Its main function is to supply blood glucose in cases of
carbohydrate deficiency (fasting, starvation and low
carbohydrate diet).
 Sites:
 Cytoplasm and mitochondria of liver and kidney
tissues (due to presence of glucose-6-phosphatase and
fructose-1,6-biphosphatase)

1- Propionic acid:
 It is the product of odd number fatty acid
oxidation by β oxidation
2- Glycerol
3-Glucogenic amino acids:
 Amino acids by deamination can be converted
into α-keto acids as pyruvic, α ketoglutaric and
OAA → they can be converted into glucose.
 Proteins are considered as one of the main
sources of blood glucose especially after 18
hours due to deplation of liver glycogen.

4-Lactic acid (Cori cycle):
 In vigorous skeletal muscle activity, large amount
of lactic acid produced → passes to the liver
through blood stream → converted in liver into
pyruvic acid and lastly to glucose→ reach muscle
once again through blood → this cycle called
Cori cycle.
 Importance of Cori cycle:
1- It prevents loss of lactate as waste products in urine.
2- Oxidation of reduced NAD.
3- It supplies red cells and contracting muscles with
glucose for reutilization and ATP production.

5- Glucose – alanine Cycle:
 During starvation there is muscle protein catabolism
→ NH3 and pyruvic acid (produced from glycosis), →
alanine is formed → reach liver and converted into
pyruvic acid which give glucose through
gluconeogenesis and NH3 which converted into urea
→ excreted in urine.
 Significant of glucose alanine cycle:
1. Disposal of NH3 produced from muscle protein
catabolism through formation of urea which excreted in
urine.
2. Prevent accumulation of lactic acid which change PH of
blood.
3. Conserve NAD/NADH-H+ ratio.
4- It supplies muscles with glucose for ATP production.

 Def.:
It is conversion of pyruvic acid and other α-keto acids
into CoA derivatives.
 Site:
In mitochondrial matrix of all tissues except RBCs.
 Enzyme:
pyruvate dehydrogenase complex which composed of
 3 enzymes act cooperative with each other
 5 co-enzymes: TPP - lipoic – acid – CoASH – FAD –
NAD
 Energy production:
NAD ---- NADH+H = 3ATP (1 mol gluc = 6 ATP)

 Def.:
It is the series of reactions in mitochondria which
oxidize acetyl CoA to CO2 , H20 and energy.
During oxidation in the cycle, hydrogens are
transferred to NAD+ and FAD then to the
respiratory chains for ATP synthesis.
 Site:
Mitochondria of all tissue cells except RBCs.
The enzymes of the cycle are present in
mitochondrial matrix except succinate
dehydrogenase which is tightly bound to inner
mitochondrial membrane

Pyruvate
FA oxid.

- Isocitrate → α-ketogluterate 3 ATP
- α-ketogluterate → succinyl COA. 3 ATP
- Succinyl CoA → succinate 1 ATP
- Succinate → fumarate 2 ATP
- Malate → O.A.A. 3 ATP
12 ATP
 Energy production from oxidation of acetyl CoA in
Kreb's cycle is 12 ATP.
 Total energy production from oxidation of pyruvic a.
is 15 ATP.
 Energy production from oxidation of glucose to CO2 +
H2O + energy is 36 or 38 ATP :
 6 or 8 ATP in glycolysis.
 6 ATP from conversion of Pyruvic to acetyl COA
 24 ATP for acetyl CoA in Kreb's cycle.

1-It is the final pathway for complete oxidation
of all food-stuffs CHO, lipids and protein
which are converted to acetyl CoA.
2. It is the major source of energy for cells
except cells without mitochondria as RBCs.
3-It is the major source of succinyl CoA which
used for:
 Porphyrine and HB synthesis.
 Ketone bodies activation.
 Converted to OAA → glucose.
 Detoxication by conjugation.

4. Synthetic functions of Kreb's cycle:
a- Amphibolic reactions.
- In fasting oxaloacetic acid is used for synthesis of
glucose by gluconeogenesis.
- In feeding state: citric acid is used for synthesis
of fatty acids.
- Reactions of Kreb's cycle are used for synthesis of
amino acid as O.A.A. →Aspartic acid and α-
ketogluterate → glutemic acid
b- Anaplerotic reactions
- O.A.A. can synthesized from pyruvic acid by
pyruvate carboxyalse which used in
gluconeogenesis.
- Aspartic acid. → O.A.A.
- Glutamic acid → α-ketogluterate

1) Flouro-acetate reacts with oxalacetate
forming flourocitrate, which inhibits the
aconitase enzyme.
2) Arsenite inhibits α-ketoglutarate
dehydrogenase.
3) Malonate acts as competitive inhibitor for
succinate dehydrogenase.

 Roles of vitamins in citric acid cycle:
1. Riboflavin, the form of FAD , cofactor in
ketoglutarate dehydrogenase complex and
in succinate dehydrogenase
2. Niacin in the form of NAD, the coenzyme
for isocitrate dehydrogenase ,α-
ketoglutarate dehydrogenase and malate
dehydrogenase
3. Thiamine : as TPP the coenzyme for
decarboxylation in α-ketoglutarate
dehydrogenase
4. Pantothenic acid as part of coenzyme A
which present in the form of acetyl-COA
and succinyl -COA

Bio l4,5

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