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Lec:3
Biochemistry
Dr. Anwar almzaiel
GLYCOLYSIS
Glycolysis is a cytoplasmic pathway that converts glucose into two
pyruvates, releasing a modest amount of energy captured in two
substrate-level phosphorylations and one oxidation reaction. If a cell has
mitochondria and oxygen, glycolysis is aerobic. If either mitochondria or
oxygen is lacking, glycolysis may occur anaerobically (erythrocytes,
exercising skeletal muscle),although some of the available energy is lost
glycogen
glucoseamine
G.1.P
Hexokinease
Glucokinase
1) Glucose
G.6.P
+2
Mg ,
Mn+2
ADP
ATP
Insulin
glycolysis
Phosphohexo
isomerase
Hexose mono
phosphate pathway
It is an allosteric enzyme.
2) G 6.P
F.6.P
(the reaction is reversible because
the energy is equal on sides (equilibrium) so if the level of G.6.P
increases or exceeds the F.6.P the G 6.P is converted to F.6.P and vice
versa).
3) F.6.P then phosphorylated and converted to fructose1,6 –diphosphate
(F.1,6 diphosphate or F.1,6 bis phosphate), by action of
phosphofructokinase which need energy so ATP
ADP and also Mg+2
+2
and MnPhosphofructokinase
are needed
F.6.P.
lactate
ATP
F.1,6 diphosphate
-, it continue
until Goes to pyruvate or
Mg+2,
Mn+2
ADP
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Biochemistry
Dr. Anwar almzaiel
-Its regulatory enzyme (allosteric) enzyme),
inhibited by ATP and citrate, and activated by AMP.
and long chain fatty acid also inhibited P enzyme
Insulin stimulates and glucagon inhibits hosphofructokinase PFK in
hepatocytes
Phosphofructokinase is another allosteric enzyme of glycolysis and
catalyzes rate
limiting reaction of glycolysis.
4) F.1,6 diphosphate now split into 2 triose: glyceraldyde-3-phosphate
and dihydroxy aceton phosphate, the reaction is reversible carried out by
aldolase
Aldolase
F.1,6 diphosphate
glyceraldeyde-3-phosphate
Dihydroxy aceton phosphate
-dihydroxy aceton phosphate is metabolised
in glycolysis unless its converted to glyceraldehyde-3 -phosphate by
phosphotriose isomerase (This reaction is reversible)
-Two molecules of glyceraldeyde-3-phosphate is
formed, molecule from glyceraldehyde-3 phosphate and other from
dihydroxy aceto phosphate, so from this point the next rea will be for 2
molecules
Dihydroxy aceton phosphate may be converted into glycerol and F.A.
Glycerol can be oxidized to give dihydroxy aceton phosphate, while fatty
acids are oxidised to acetyl COA which enters Citric acid cycle
For example, when someone eats any rice, he will be a fat due to
accumulation of fat, rice is a carbohydrate which is converted into
glycerol and F.A and stored as fat. During fasting fat is changed into
glycerol and F.A to supply energy by conversion to aceton dihydroxy
phosphate (pioint of junction with fat metabolism)
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Biochemistry
Dr. Anwar almzaiel
5) glyceraldeyde-3-phosphate is converted into glyceric acid 1,3
diphosphate by the action of glyceraldehyde 3 phosphate dehydrogenase.
The reaction is reversible and involves the conversion of NAD+ into
NADH, the removal of hydrogen (oxidation) causes dehydrogenation and
we have also energy released in the form of Pi group, glyceric acid 1,3
diphosphate high energy compound. If glycolysis is aerobic, the NADH
can be reoxidized (indirectly) by the mitochondrial electron transport
chain, providing energy for ATP synthesis by oxidative phosphorylation
.
glyceraldehyde 3 phosphate
dehydrogenase
Pi
glyceraldeyde-3-phosphate
NAD+
NADH+H
glyceric acid 1,3
diphosphate
glyceraldehyde 3 phosphate dehydrogenase enzyme made of 4 subunits
contains sulfhydro group, it is inhibited by mercury (Hg), iodoacetate and
arsenate
How does NAD work?
The active form NAD+ draws 2 hydrogen atoms, one of them attached to
NAD+ and the other will loss an electron causing the NAD+ to be
neutrilized and this hydrogen atom will be positively charged because it
loses an electron the NAD+ as result will be NADH. H+
NADH. H+ can be reoxidized by converting pyruvic acid into lactic acid,
for this reason, glycolysis is an anaerobic oxidation process because it
does not need energy due to the action of NAD.
5) Fate of 1,3 diphosphoglyceric acid: During glycolysis the 1,3
diphosphoglyceric acid enters two pathways
Phosphoglceric kinase
a. 1,3 diphosphoglyceric acid + 2ADP
phosphoglyceric acid +2ATP
3-
1,3 diphosphoglyceric acid has a high energy can be given to ADP
and with Pi group f 2 molecules of ATP will form and then
conversion of 3 phosphoglyceric into 2-phosphoglyceric by
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Biochemistry
Dr. Anwar almzaiel
phosphoglyceric mutase and then continue glycolysis. The
reaction is reversible (no loss of energy)
diphosphoglyceric acid mutase
b. 1,3 diphosphoglyceric acid
2,3
diphosphoglyceric acid
Production of 2,3 diphosphophate glyceric acid by glycolysis by a
specific mutase and this found in RBC along the normal glycolysis.
Large amount of 2,3 diphosphoglyceric acid are produced in
human RBC, it plays an important role in regulation of oxygen
binding and release by Hb. It lowers the oxygen tension in RBC
and thus causes release of O2 to tissue (no energy was produced).
6) Following conversion of 1,3 diphosphoglyceric acid into
glyceric acid 3 phosphate, the latter is converted into glyceric acid
2 phosphate by mutase
The reoxidation of NADH.H+ into NAD+ can be accomplished by the
following reactions:
Pyruvate
NADH++H
lactate (lactic acid)
NAD+
glyceraldeyde-3-phosphate
glyceric acid 1,3 diphosphate
NAD+
NADH++H
6) Fate of 1,3 diphosphoglyceric acid: During glycolysis the 1,3
diphosphoglyceric acid enters two pathways
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Biochemistry
a. 1,3 diphosphoglyceric acid + 2ADP
phosphoglyceric acid +2ATP
Dr. Anwar almzaiel
3-
1,3 diphosphoglyceric acid has a high energy can be given to ADP
and with Pi group 2 molecules of ATP will form and then
conversion of 3 phosphoglyceric into 2-phosphoglyceric by
phosphoglyceric mutase and continue glycolysis. The reaction is
reversible (no loss of energy)
Diphosphoglyceric mutase
b. 1,3 diphosphoglyceric acid
diphosphoglyceric acid
acid mutase
2,3
Production of 2,3 diphosphophate glyceric acid by glycolysis by a
specific mutase and this found in RBC along the normal glycolysis.
Large amount of 2, 3 diphosphoglyceric acid are produced in
human RBC, it plays an important role in regulation of oxygen
binding and releasing by Hb. It lowers the oxygen tension in RBC
and thus causes release of O2 to tissue (no energy was produced).
The 2,3 diphosphate glyceric acid hydrolysed and converted into
glyceric 2 phosphate without ATP molecules and thus in this
secondary pathway no release of energy occurs since 2 ATP is used
in the conversion of glucose into glucose 6 phosphate and fructose
into fructose 1,6 diphosphate and 2 ATP are released in the
conversional of PEP into pyruvic acid
Medical Importance
1. In the erythrocytes 2, 3-diPG aids unloading of oxygen by
oxyhaemoglobin.
2. Due to the diversion of 1, 3-BPG to 2, 3-BPG production, energy yield
of glycolysis is less in erythrocyte
2,3-di( bis) Phosphoglycerate Cycle
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Dr. Anwar almzaiel
7) Following conversion of 1,3 diphosphoglyceric acid into glyceric acid
3 phosphate, the latter is converted into glyceric acid 2 phosphate by
mutase (mutase mean mutarotation changes the position of
phosphate group)
mutase
Glyceric acid 3 phosphate
phosphate
Glyceric acid 2
8) Glyceric acid 2 phosphate loss H2O molecule in a reversible reaction
and no loss of energy to give phosphoenol pyruvate which has energy can
be given to ADP to form ATP in an irreversible reaction to form pyruvic
acid.
Enolase
Glyceric acid 2 phosphate
Phosphoenol pyruvate
9) Phosphoenol pyruvate has high energy (1200 cal) can be given to ADP
to form ATP in an irreversible reaction to form pyruvic acid
Puruvate kinase
Phosphoenol pyruvate
ADP
Pyruvate
Mg+2,
Mn+2
ATP
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Biochemistry
Dr. Anwar almzaiel
10) In absence of oxygen pyruvic acid converted into lactic acid by action
of lactic acid dehydrogenase enzyme and the NADH the reaction gives up
NAD + which enters the cycle again and used for conversion of
glyceraldeyde-3-phosphate into glyceric acid 1,3 diphosphate. In
presence of oxygen, pyruvate continues in the mitochondria and burned
into CO2, H2O and ATP
Lactate dehydrogenase
Pyruvate
Lactate
NADH + H+
Glyceraldeyde-3-phosphate
NAD+
Glyceric acid 1, 3
diphosphate
This reaction occurs under anaerobic conditions. Formation of lactate
using NADH as hydrogen donor is essential for the continuation of
glycolysis in rapidly contracting skeletal muscle and erythrocytes because
NADH can not be oxidized by respiratory chain O2
been reduced to NADH. By reducing pyruvate to lactate and oxidizing
NADH to NAD, lactate dehydrogenase prevents this potential problem
from developing. In aerobic tissues, lactate does not normally form in
significant amounts. However, when oxygenation is poor (skeletal muscle
during strenuous exercise, myocardial infarction), most cellular ATP is
generated by anaerobic glycolysis,and lactate production increase
Energetics of Glycolysis
Generation and consumption of ATP in anaerobic and aerobic glycolysis
is given below.
In aerobic glycolysis:
1. Number of ATPs generated by phosphoglycerate kinase 2
2. Number of ATPs generated by Pyruvate kinase 2
3. Number of ATPs generated by respiratory chain
oxidation of 2 NADH produced in reaction 6 6
4. Number of ATPs consumed in reaction 1 and 3 –2
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Biochemistry
Dr. Anwar almzaiel
Net = 8
In anaerobic glycolysis
2 NADH produced in reaction 6 are used to convert pyruvate
to lactate. Hence, ATP is not generated. Therefore, the net ATP
production in anaerobic
glycolysis is only 2 (8 – 6 = 2). Thus, oxidation of glucose to pyruvate
(aerobic glycolysis)
generates 8 ATP molecules whereas oxidation of glucose to lactate
(anaerobic glycolysis)
generates 2 ATP molecules.
Medical and Biological Importance of Glycolysis
1. Glycolysis provides energy to cells. Anaerobic glycolysis meets energy
requirement of rapidly contracting skeletal muscle.
2. Since heart is mainly aerobic organ, myocardial ischemia decreases
glycolytic ability of cardiac muscle. As a result energy or ATP production
in heart is affected.
3. Deficiency of enzymes of erythrocyte glycolysis (pyruvate kinase)
causes haemolytic anemia. This is because erythrocytes gets their energy
from glycolysis.
4. Deficiency of muscle phosphofructo kinase causes decreased muscular
performance and fatigue.
5. Dietary fructose and galactose are also metabolized by this pathway.
6. Glycolysis has amphibolic role also. It provides precursors for the
formation of lipids
and aminoacids. For example, pyruvate is converted to alanine by
transaminationand dihydroxy acetone phosphate serves as precursor for
triglyceride formation.
7. Two glycolytic intermediates pyruvate and glyceraldehydes-3phosphate are used for the synthesis of cholesterol, thiamine and
pyridoxine in tuberculosis, malaria and gastritis causing organisms.
Regulation of Glycolysis
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Dr. Anwar J Almzaiel
Usually metabolic pathways are regulated by altering activities of few enzymes
of that
pathway. Glycolysis is under :
-allosteric control
- hormonal control.
regulatory enzymes of glycolysis
Hexokinase , phosphofructokinase and pyruvate kinase are. Their activities are
allosterically controlled.
Gucokinase, phosphofructokinase-1 and pyruvate kinase are under hormonal
control also.
Allosteric regulation of glycolysis
Phosphofructokinase-1 is the major regulatory enzymes of glycolysis. It is an
allosteric enzyme and catalyzes rate limiting reaction of glycolysis. It is
inhibited by ATP and citrate. AMP and fructose-6-phosphate are activators of
this enzyme. Pyruvate kinase is the second regulatory enzyme. It is inhibited by
ATP and phosphoenolpyrvate. Glucose-6-phosphate inhibits activity of
hexokinase. So, when ATP (energy) concentration is high
glycolysis is inhibited and decrease in ATP level increases rate of glycolysis.
Hormonal regulation of glycolysis
Insulin increases rate of glycolysis by increasing concentration of glucokinase,
phosphofructokinase-1 and pyruvate kinase
Puruvic acid Kinase
Its irreversible enzyme under physiological condition and it is regulatory
enzyme, it require Mg++, Mn++, Thus it will form complex before bind to
substrate this enzyme is activated by by fructose 1,6 diphosphate and
phosphoenolpyruvate
 It is activated by presence of high concentration of fructose 1,6
diphosphate and the reaction will continuous forward and also activated
by a high level of phosphoenol pyruvate
 It is inhibited by the presence of high level of ATP, pyruvic acid, citrate,
alanine (alanine is converted into puruvate).
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Dr. Anwar J Almzaiel
It is 3rd mechanism of regulation, thus mechanism of regulation involve:
i) Regulation of hexokinase in the converting of glucose into glucose-6phosphate
ii) Regulation phosphofructokinase in the converting of fructose-6phosphate into 1,6 diphosphate
iii) Regulation of pyruvate kinase in the formation of pyruvate
Biological lesion for pyruvic kinase deficiency
The deficiency of pyruvic acid kinase is classified (in RBC) as congenital
non spherocytic haemocytic anaemia, it leads to low ATP production in
RBC and its prematurated death. The lysis of RBC decreases with an
increase in glucose and ATP. By the action of autosomal recessive genes,
the enzyme is absent in RBC heterozygous which carry half the normal
amount of the enzyme, this is treated by increase the glucose level and
ATP level in RBC
Lactic acid dehydrogenase
It converts pyruvic acid to lactic acid which involves reoxidation of
NADH formed in oxidation of glyceraldeyde 3 phosphate. LDH exists in
the body as an isoenzyme in the intracellular compartment of pH= 8.6
and molecular weight=130000. It acts as isoenzyme (has different net
charge and migrate to different regions in electric field). There are 2 types
of this enzymes existing in the tissue and each of them contains
sulfahydryl group-SH
These 2 types are:
1- HLDH: produced in heart
2- MLDH: produced in liver and skeletal muscle
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Dr. Anwar J Almzaiel
These 2 will form 5 active enzymes each contain 4subunit
LDH
isoenzyme
LDH1
LDH”
LDH3
LDH4
LDH4
HHHH
HHHM
HHMM
HMMM
MMMM
H4
H3M
H2M2
HM3
M4
Heart
RBC
60
33
70
Trace<1
Trace<1
42
44
10
4
Trace
Skeletal
muscle
4
7
17
16
56
Liver
2
6
13
13
64
Tissue contains mixture of these isoenzymes, M subunits are more susceptible
to high temperature and other denaturating agents than H subunits, treatment of
sample with denaturating agents will destroy M4 and M3H and loss of LDH
activity upon heating has been used as an index of relative isoenzyme activities
damage in cell permeability or destruction, the serum LDH level is elevated and
the
Treatment
Source of activity
Untreated serum
LDH1-LDH5
Serum heat to 57
LDH1-LDH4
Serum heat 65
LDH1
Heart muscle works under aerobic condition has primarily isoenzyme made up
of 1 subunit (H) so tissue produce very little lactate because :
 Pyruvic acid formed in glycolysis is oxidised by heart tissue into CO2,
H2O and ATP to maintain heart mechanical work. This happens because
lactate inhibits (H) isoenzyme of LDH as result the enzyme is used to
convert lactate into pyruvate in heart cell acid
Immediately used by heart
LDH, H1 type
Lactate
puruvate
Energy to
continue
mechanical work
of hart
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Fate of Pyruvate
Under aerobic conditions, pyruvate is converted to acetyl-CoA in all tissues
containing mitochondria. Both pyruvate molecules are oxidized to two acetylCoA molecules.
Entry of Pyruvate into Mitochondria
In mitochondria, pyruvate undergoes oxidative decarboxylation and remaining
two carbon fragment is converted to acetyl-CoA. The reaction is irreversible
and multi-step process. This reaction is catalyzed by pyruvate dehydrogenase
(PD) multi enzyme complex present in inner mitochondrial membrane. This
multi enzyme complex consist of three enzymes.
. The conversion of pyruvic acid to acetyl COA involves 5 types of reaction and
each reaction is catalysed by different enzyme system these enzymes act as a
multi enzyme system (complex)..
Regulation of Pyruvate Dehydrogenase
Pyruvate dehydrogenase activity is regulated by
1. Feedback inhibition.
2. Covalent modification. Acetyl-CoA and NADH inhibits activity of pyruvate
dehydrogenase.
3.Increase in level of ADP or AMP so the cell needs energy and in order to gain
energy citric acid cycle must be activated and this cycle needs acetyl COA
which it gets from the activation of pyruvate dehydrogenase
This enzyme is found in the cell in two forms:-Inactive (if phosphorylated)
-Active (when dephosphorylated)
Phosphorylation and dephosphorylation of this enzyme is under hormonal
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control Insulin increases its activity by favoring dephosphorylation.
Medical Importance
1. Pyruvate dehydrogenase serve as a link between aerobic glycolysis and citric
acid cycle.
2. Since the reaction catalyzed by this enzyme is irreversible, acetyl -CoA can
not be converted to pyruvate.
3. Lactic acidemia occurs in some individuals due to deficiency of pyruvate
dehydrogenase.
4. Arsenic compounds inhibits this enzyme by reacting with-SH of lipoic acid.
War gases and pesticides containing arsenic inhibit this enzyme. Deaths due to
arsenic poisoning are well documented in history.
Fate of Acetyl-CoA
-The body used acetyl COA to form fatty acids, so when a person eats any high
carbohydrate diet there will be formation of fatty acids which are stored in the
form of lipid glycerol and triglycerides, while during fasting triglycerides
converted into fatty acids and acetyl COA that enters citric acid cycle
- Another fate of Acetyl COA is the formation of cholesterol in liver which is
converted into Vit-D, steroid hormones and bile acids and salts that are of great
important in the digestive system
Citric Acid Cycle
1. Cyclic arrangement of sequence of reactions that convert acetyl-CoA to two
molecules
of CO2 is called as citric acid cycle.
2. It is also called as Tricarboxylic acid (TCA) cycle or Krebs cycle.
3. This cyclic process starts with oxaloacetate and completes with regeneration
of oxaloacetate.
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4. The conversion of acetyl-CoA to CO2 in the citric acid cycle generates
reducing equivalents (NADH, FADH2) and GTP.
5. The reduced co-enzymes are finally oxidized in the respiratory chain with
concomitant generation of ATP.
6. One acetyl-CoA molecule is oxidized by this cycle at a time.
Site
Enzymes of citric acid cycle are present in mitochondrial matrix
Citric acid cycle pathway
1- Acetyl COA condense with oxaloacetate which can be obtained either
from pyruvate or from deamination of aspartate. Citrate is formed by the
action of citrate synthase this reaction needs energy and this energy
comes from hydrolysis of thioester linkage of acetyl COA. This enzyme
can control the citric acid cycle so its inhibited by
 High level of NADH, because this reaction needs drawing of H and when
there is a high level of NADH, no drawing occur and it will stop
 High level of succinyl COA
 High level of ATP
 Long chain fatty acids
1- As citric acid (citrate) is formed, it will be converted into isocitrate this
occur by the action of Aconitase enzyme, which draws H2O from citric
acid forming Aconitic acid (Cis-aconitate) this compound by the action of
the same enzyme will take H2O and thus converting into isocitric acid
(isocitrate).
This reaction is (reversible) so when level of isocitrate increases, it will
return forming citric acid (but usually proceeds forward because of the
continuous removal of isocitrate from medium)
2- Once isocitric acid (isocitrate) formed, it will converted into
oxalosuccinic acid by the action of isocitrate acid dehydrogenase which
needs NAD to draw H and converts it to NADH, then by the action of
same enzyme CO2 is removed from oxalosuccinate which is converted
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into α ketoglutarate. This enzyme can control the cycle and there are two
types of this enzymes.
1st type : - present in the cytoplasm
- nonallosteric enzyme
- requires different co-factor which is NAPD
2nd type :-a- found in mitochondria (called mitochondrial enzyme)
b- allosteric enzyme
c- activated by high level of ADP and NAD
inhibited by high level of ATP and NADH
When α-keto glutarate formed, we have a point of junction with amino acids
catabolism, because if α-keto glutarate takes amino group, it will converted into
glutamic acid which can loss amino group again and returns to α-keto glutarate
(so it can be used in the synthesis of some amino acids (non-essential amino
acids)) when α-keto glutarate it will formed by deamination of glutamic acid
3- α-keto glutarate undergoes dehydrogenation and decarboxylation to yield
succinyl COA by action of α-keto glutarate dehydrogenase which needs
NAD to draw H and form NADH. In this reaction energy is released and
stored in succinyl COA. This reaction which is oxidative dehydrogenase
is catalysed by multi enzyme complex (like pyruvate dehydrogenase) and
needs the same cofactors (TPP, COA, Mg, NAD, FAD).
4- Succinyl COA is converted into succinate by the action of succinate
synthase (thiokinase) this results in releasing energy which taken by ADP
to give ATP (the 1st ATP formed in the cycle and can be used by the body
5- Now succinate will be undergo molecular arrangement, so it is converted
into fumeric acid (fumerate) by action of succinate dehydrogenase which
need a carrier of H called FAD that takes H and converts to FADH2
6- Fumarate will take H2O by fumerase enzyme and converted into malate,
then malate is converted into oxaloacetate by the action of malate
dehydrogenase which need NAD to draw H and give NADH
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The citric acid cycle starts with oxaloacetate and acetyl COA and ends
with oxaloacetate and acetyl COA which released in the form of CO2,
NADH, FAD and ATP
Small amount of energy released directly in the form of ATP in citric acid
cycle, but in NADH which is produced can oxidized to H2O and produce
high energy by respiratory chain through biological oxidation
Energetics of Citric Acid Cycle
Oxidation of acetyl-CoA in citric acid cycle is expressed as single equation
below.
Acetyl COA+ GDP +Pi +3NAD+FAD
2CO2 +CoASH+GTP
+3NADH+3H+FADH2
Acetyl CoA +2O2+12Pi +12ADP→2CO2 +12ATP+CoASH+13H2O
Generation of ATP in Citric Acid Cycle
1. Number of ATP generated by oxidation of 3 NADH
2. Number of ATP generated by oxidation of FADH2
3. Number of ATP generated from GTP
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9
2
1
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For 2 acetyl COA ----------------24ATP
Pyruvic acid
acetyl COA
2NADH
6ATP
The net result 30 ATP from oxidation of acetyl COA
ATP produced from metabolism of one molecule of glucose
A- Aerobic condition (in presence of O2)
Glycolysis
per molecule
Energy produced reaction
 2glyceraldhyde-3-phosphate
2glyceric acid 1,3 diphosphate
 2glyceric acid 1,3 diphosphate
2(3 phosphoglycerate)
 2phospoenol pyruvate
puruvate
N of ATP
2NADH(6ATP)
2ATP
2ATP
Net 10ATP
2ATP used in
Glucose
8ATP
glucose-6-phosphate
Fructose-6- phosphate
Fructose-1,6-diphosphate
So that net result will be 8ATP and 2 pyruvate molecules enter citric acid cycle
In cireic acid cycle:
30ATP
The total ATP molecules from the oxidation of 1 molecule of glucose under
aerobic condition is 38 ATP
B- Anaereobic condition (anaerobic glycolysis)
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Overall reaction:
Glucose + 2Pi +ADP
2 Lactate + 2ATP + 2H2O
- Two molecules of ATP are generated for each molecule of glucose
converted to lactate
- In anaerobic glycolysis there is no net production or consumption of
NADH formed of NADH
- 2 molecules of lactate is produced for each glucose molecule
metabolized
- Glycolysis in present of O2 give
8ATP
Glycolysis in absence of O2 give
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Metabolism of glycogen
Glycogen is the major storage form of carbohydrate in animal and corresponds to
starch in plant. It occurs mainly in liver (up to 6%) and muscle(up to 1%).
However, because of great mass, muscle represents some 3-4 times as much as
glycogen store as liver. Like starch it is branched polymer of α- glucose.
The function of muscle glycogen is to act as a readily available source of hexose
units for glycolysis within the muscle itself. Liver glycogen is largely concerned
with storage and export of hexose units for maintenance of the blood glucose,
particularly between meals. After (12-18 hours) of fasting, the liver becomes
almost totally depleted of glycogen, whereas muscle glycogen is only depleted
significantly after prolonged various exercise.
Why the cell can store glycogen but not glucose?
Because when glucose increased, osmatic pressure in the cell increase, causing
water movement toward the cell and leading to burst so when glucose accumulates
in the cell, it will convert to glycogen which consists of branched series of
glucose.
Glycogenesis
The process of glycogenesis start when glucose-6-phosphat is changed to glucose1-phosphate by mutase
mutas
e glucose1,6diphosphate
mutas
e glucose 1-phosphate
glucose-6-phosphat
the reaction is reversible and depends on concentration of substrate (glucose-6phosphat), if there is a large amount or quantities of glucose-6-phosphat will lead
to formation of glucose 1-phosphate and the opposite is right. No loss in the
energy in this reaction
 As glucose 1-phosphate formed, it will react with high energy compound UTP
(uradin triphosphate), which react with glucose to give UDP glucose (uradin
diphosphate glucose) and pyrophosphate released
 glucose 1-phosphate is high energetic compound and called (active glucose
molecule), this reaction is carried by (UDP glucose pyrophosphorylase)
 one UDP glucose is formed ,it can add already to exiting glycogen in the cell
(glycogen primer) by addition of α1-4 linkage causing elongation of the chain
is carried by glycogen synthase
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
In the same time (simultaneously) another enzyme will change α1-4 linkage to
α1-6 linkage, this enzyme (Amylo α1-4
α1-6 linkage trans glucosidase or
branching enzyme.
The process continues by addition of more glucose molecules at α1-4 linkage
and then changing this to α1-6 linkage as result a large glycogen molecule
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Glycogen synthase
Found in the cell in active or inactive form
Glycogen synthase
Inactive form
glycogen synthase
active form
+ PO4
- PO4
Glycogen synthase kinase (active)
ADP
ATP Adenyl cyclase
ATP
cAMP
adrenalin
Glycogen synthase kinase (inactive)
Glucagon
Adenyl cyclase is activated by:
1- Adrenalin hormones
2- Glucagon hormones
-
So the inactive glycogen synthase is activated by losing phosphate group
and gives it to ADP molecule to form ATP
-
The reaction is carried out by the glycogen synthase phosphatase enzyme
which activated by insulin, so high concentration of glucose will cause
activation of glycogen synthase
-
Active glycogen synthase become inactive when it takes phosphate group
and thus is converted to ADP
-
The reaction is carried by the enzyme glycogen synthase kinase (active),
this phosphate group is attached to (OH) group of enzyme
- Also glycogen synthase kinase is found active or inactive
Inactive one is activated by cAMP (cyclic AMP) or 3,5 cyclic AMP that is
formed within the cell from ATP by the action of adenyl cyclase enzyme,
its activated by adrenalin and glucagon hormones
During exercise or emotional stress, adrenalin is released in very high concentration
activating the formation of cAMP and then glycogen synthesis is inhibited while a
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Dr. Anwar almzaiel
high amount of glucose will be used by the body to produce high amount of energy,
when it necessary for the exercise or emotional stress.
H2O
cAMP
5AMP
Phosphodiesterase
Activation by insulin
+
Inhibited by caffeine
Glycogen synthase is activated by glucose-6 phosphate and inhibited by glycogen
(allosteric enzyme)
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