Glucose Metabolism(Glycolysis)

❑ Color Index:
➢ Original slides.
➢ Original slide : for enzyme
➢ Important.
:‫رابط التعديل‬
➢ 436 Notes https://docs.google.com/document/d/1WvdeC1atp7
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ZKWOUSukSLsEcosjZ0AqV4z2VcH2TA0/edit?usp
➢ 438 notes =sharing
➢ Extra information Biochemistry team 438
 Objectives:
● Recognize glycolysis as the major oxidative pathway of glucose
● List the main reactions of glycolytic pathway
(there are 10 reactions)
● Discuss the rate-limiting enzymes/Regulation
● Assess the ATP production (aerobic/anaerobic)
● Define pyruvate kinase deficiency hemolytic anemia
● Discuss the unique nature of glycolysis in RBCs.
Dr’s Notes:
You must know:
- location: cytosol
- Net yield
- Substrates & products
 Overview
• Glycolysis, the major pathway for glucose oxidation, occurs in
the cytosol of all cells.
• It is unique, in that it can function either aerobically or
anaerobically, depending on the availability of oxygen and
intact mitochondria.
• It allows tissues to survive in presence or absence of oxygen,
e.g., skeletal muscle.
• RBCs, which lack mitochondria, are completely reliant on
glucose as their metabolic fuel, and metabolizes it by
anaerobic glycolysis.
 Reversible =

Irreversible =

Glycolysis

Aerobic Anaerobic

Available both : O2 & Absence of O2 or

MITOCHONDRIA mitochondria or
both of them
End product: Pyruvate
End product: Lactate
Aerobic
Isomerization of Phosphorylation
Phosphorylation
glucose of fructose
of glucose
6- phosphate 6- phosphate

Oxidation of Isomerization of Cleavage of

glyceraldehyde dihydroxyaceton fructose 1,6-
3- phosphate e phosphate bisphosphate

Synthesis of 3-
phosphoglycerat Shift of the Dehydration of 2-
Short cut: PEP e, producing phosphate group phosphoglycerate
ATP

Formation of
pyruvate,
producing ATP
 1st reaction 2nd reaction
Phosphorylation of glucose Isomerization of glucose 6-phosphate

1-ACTION :
Adding of 2-ACTION :
phosphate Isomerization
group to 1 ATP is
glucose consumed*
In the liver
Enzymes : of glucose 6-
Hexokinase: phosphate to
Most tissues fructose 6-
Glucokinase: phosphate
Hepatocyte Enzyme :
Phosphoglucose
isomerase
1 ATP is consumed*
Regulation: Glucokinase/Hexokinase

Hexokinase isoforms
(4 isoforms )

3 Hexokinase 1 Glucokinase

In tissues In liver & pancreas

it is inhibited by the reaction product, It is inhibited indirectly by Fructose-
glucose-6-P which accumulates when 6-P and is indirectly stimulated by
further metabolism of this hexose is glucose
reduced
 Glucokinase (GK) Regulation
• In the presence of high fructose-6-phosphate, GK translocates
and binds tightly to GKRP (glucokinase regulatory protein) in
the nucleus, making it inactive

• When glucose levels are high in blood and hepatocytes

(GLUT-2), GK is released from GKRP and enters the cytosol
Reactions (3rd -5th)

Phosphorylation of fructose 6-phosphate

1 ATP is consumed*

ACTION :
Adding phosphate group to fructose 6-phosphate

Enzyme : Phospho-fructokinase-1 (PFK-1)

*Phospho-fructokinase-1 (PFK-1) is the most important

regulatory enzyme in glycolysis* .
It’s a rate limiting enzyme

(PFK-1) and its regulation

● Allosteric Regulation
Inhibited by: ATP & citrate
Stimulated by: AMP & Fructose2,6-bisphosphate
‫ممكن يأخذ الجسم ثنين من واحد منهم‬
● Induction/Repression ‫يعني؟؟ يحول واحدة منهم لثاني الن هذا تفاعل رجعي‬
Induced by: insulin ‫او ينتج ثنين اللي هو محتاجه بيسويه‬
‫بس حنا ندرس لما يكون‬
Repressed by: glucagon 2 Glyceraldehydes
Reactions (3rd-5th)
Isomerization of
Cleavage of fructose dihydroxyacetone
1,6- bisphosphate phosphate
ACTION : ACTION :
Cleaving fructose 1,6-bisphosphate Interconverting dihydroxyacetone
to dihydroxyacetone phosphate phos- phate (DHAP) into
and glyceraldehyde 3-phosphate glyceraldehyde 3- phosphate
Enzyme: Enzyme:
Aldolase A Triose phosphate isomerase

● To complete glycolytic pathway (DHAP) should be converted to glyceraldehyde 3-

phosphate, so we will have 2 molecules of glyceraldehyde 3-phosphate
● After this point there will be 2 molecules of the each next reactions
(Reactions: 6th – 10th)
‫ ال نحبذ التحدث بها كعيال‬10-6 ‫االنزيمات في التفاعالت‬
Synthesis of 3-
Oxidation of glyceraldehyde phosphoglycerate,
3- phosphate
x2
Producing ATP
(Oxidative level) (Substrate level)
ACTION : ACTION :
Oxidation to the molecule NAD+ Phosphate group add to ADP to
NADH , this reaction used to add become ATP.
Phosphate group to the molecule. x2
Enzyme : Enzyme : Phosphoglycerate kinase
Glyceraldehyde 3-phosphate
Dehydrogenase.

x2
(Reactions: 6th – 10th)
“last 3”
‫ ال نحبذ التحدث بها كعيال‬10-6 ‫االنزيمات في التفاعالت‬
Shift of the phosphate group
ACTION
It is isomer and what change is :
The P group change position
from O in carbon-3 to O in Dehydration of 2-
carbon-2 by
Enzyme: phosphoglycerate mutase.
phosphoglycerate
Formation of pyruvate,
producing ATP
(Substrate-level)
Enzyme: Enolase

Enzyme: pyruvate kinase

 This slide is important
Substrate-level phosphorylation it may come in SAQ

Vs.
Oxidative phosphorylation
● Phosphorylation is the metabolic reaction of introducing a phosphate group into an
organic molecule.

Oxidative phosphorylation Substrate-level phosphorylation

The formation of high-energy phosphate bonds The formation of high-energy phosphate bonds
by phosphorylation of ADP to ATP by phosphorylation of ADP to ATP
(or GDP to GTP)
the transfer of electrons from reduced cleavage of a high-energy metabolic
coenzymes to molecular oxygen by ETC intermediate (substrate).
mitochondria cytosol or mitochondria
 This slide is important

Glucokinase
Hexokinase

Regulatory Enzymes
PFK-1

Pyruvate
kinase Allosteric
Regulation of Glycolysis regulation
PFK-1
Rapid, short-term

Regulatory Covalent
Mechanisms modification

Slow, long-term Pyruvate kinase

Pyruvate Kinase Deficiency Hemolytic Anemia
PK mutation may lead to :
Altered Enzyme Kinetics
Decreased Enzyme stability
Induction: Repression:
Altered response to activator
insulin glucagon
Aerobic Glycolysis: ATP Production

ATP Consumed: 2 ATP

ATP Produced:
• Substrate-level: 2 X 2 = 4 ATP
• Oxidative-level: 2 X 3 ATP (each NADH = 3 ATP will be produced)= 6 ATP

Total: 10 ATP
Net:10–2=8ATP
Anaerobic
Isomerization of Phosphorylation
Phosphorylation
glucose of fructose
of glucose
6- phosphate 6- phosphate

Oxidation of Isomerization of Cleavage of

glyceraldehyde dihydroxyaceton fructose 1,6-
3- phosphate e phosphate bisphosphate

Synthesis of 3-
phosphoglycerat Shift of the Dehydration of 2-
● The final product of anaerobic e, producing phosphate group phosphoglycerate
glycolysis is lactate
● transforming Glyceraldehyde 3-P to
ATP
1,3-bisphosphoglycerate in anaerobic
glycolysis they go to transform reduction of
pyruvate into lactate by the help of pyruvate, formation
lactate dehydrogenase
of lactate
Anaerobic glycolysis

● NADH produced cannot be used by ETC for ATP

production (No O2 and/or No mitochondria)
● Less ATP production, as compared to aerobic glycolysis
● Lactate is an obligatory end product,

Why?
Because the cell has limited amount of NAD+. So NAD+ is
needed to transform Glyceraldehyde 3-P to 1,3-
bisphosphoglycerate and NADH molecules are produced.
Therefore, they need to be regenerated to NAD+ otherwise
glycolysis stops .
Lactate dehydrogenase

ACTION :
Pyruvate lactate
Enzyme :
● Lactate dehydrogenase The enzyme used the NADH
This reaction is
reversible. However, the
enzyme for both
directions is lactate
dehydrogenase even
though the reaction in
the forward direction
gains hydrogen
Anaerobic Glycolysis: ATP production

ATP Consumed: 2 ATP

ATP Produced:
• Substrate-level: 2 X 2 = 4 ATP
• Oxidative-level: 2 X 3 = 6 ATP
Oxidative
phosphorylation is
cancelled because the
NADH molecules don't Total: 4 ATP
go to ETC to produce
ATP in anaerobic Net: 4 – 2 = 2 ATP
glycolysis but they go to
help in lactate production
 Anaerobic Glycolysis in RBCs
All the steps are the same with other anaerobic glycolysis
except “2,3-BPG Shunt” in sometimes.

Function of: 2,3-BPG: delivery of oxygen

 ACTION :
1,3-bisphosphoglycerate→
Importance of mutase enzyme
2,3-bisphospoglycerate

Enzyme :
It is important for association Mutase
and dissociation between O2
and hemoglobin.
ACTION :
2,3-bisphospoglycerate→
Increase in “2,3-BPG” will help
3-phospoglycerate , by
to loss of association between
adding water molecule and
O2 and hemoglobin and will
removing phosphate group
release more O2.
Enzyme : phosphatase

It usually occurs with people

who live in high altitude.
 Glycolysis in RBCs: ATP Production
ATP consumed : 2 ATP
ATP produced :
Substrate-level 2X2= 4 ATP
Or 1X2= 2 ATP if the is 2,3-BPG
Total : 4 ATP
Net : 4-2= 2 ATP
Or 2-2= 0 ATP if the is 2,3-BPG

Glycolysis in RBCs: Summary

PKD
End Energy haemolytic
product yield anaemia
depend on

● Lactate Without 2,3 Degree of

● No net BPG: 2 ATP PKD
production or
consumption With 2,3 BPG Compensation
of NADH shunt: 0 ATP by 2,3-BPG
 This slide is important

Glycolysis net yield

Glycolysis
Aerobic glycolysis 8 ATP
Anaerobic glycolysis 2 ATP
Glycolysis in RBCs
Without 2,3 BPG synthesis 2 ATP
With 2,3 BPG synthesis 0 ATP
Take Home Messages
● Glycolysis is the major oxidative pathway for glucose
● Glycolysis is employed by all tissues
● Glycolysis is a tightly-regulated pathway
● PFK-1 is the rate-limiting regulatory enzyme
● Glycolysis is mainly a catabolic pathway for ATP production, But it
has some anabolic features (amphibolic)
● Pyruvate kinase deficiency in RBCs results in hemolytic anemia
● Net energy produced in:
Aerobic glycolysis: Anaerobic glycolysis:
8 ATP 2 ATP
● Net energy produced in glycolysis in RBCs:
Without 2,3 BPG synthesis: With 2,3 BPG synthesis:
2 ATP 0 ATP
 Review

Glycolysis is a type of anaerobic (does not directly require oxygen)

cellular respiration that breaks glucose down into two ATP molecules and
pyruvic acid (also called pyruvate) and releases electrons. Glycolysis
happens in the cytoplasm of the cell. The electrons that are released in
the process are picked up by NAD+ molecules and carried to another part
of the cell for another reaction called the electron transport system.
Glycolysis is the first step of a series of steps that produces ATP for
cellular energy. The pyruvic acid produced by glycolysis is then
transferred into another process called the krebs cycle where even more
ATP is made.
 MCQs
Q1; Which of the following biochemical Q2; Where does glycolysis take place?
pathways does NOT require oxygen?

A-The mitochondria
A-glycolysis B-The chloroplast
B-krebs cycles C-The cytoplasm
C-electron transport system

Q3; What is the overall end product

Q4; Which 3-carbon molecule is one
of the final products of glycolysis?
of the proccess of glycolysis?
Answer key:
A-Two extra ADP A- glucose 1-A

B-four extra ATP B- pyruvate 2-C

3-C
C-Two extra ATP C-ATP 4-B
 SAQs
Q1- What is the net production of ATP, pyruvate, and NADH when
one molecule of glucose undergoes glycolysis?
2 ATP, 2 NADH and 2 pyruvate

Q2- what is the Glycolysis?

Glycolysis is a type of anaerobic (does not directly require oxygen) cellular
respiration that breaks glucose down into two ATP molecules and pyruvic acid (also
called pyruvate) and releases electrons. Glycolysis happens in the cytoplasm of the
cell.
❖Team leaders:
‫ديما المزيد‬
‫رائد العجيري‬

@Biochemistry438
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