CARBOHYDRATE METABOLISM

glycolysis
Biochemistry 2
Code (4131 )
By the end of this lecture, students are expected to:

❑ Discuss glycolysis.

❑ List the main reactions of glycolytic pathway

❑ Define the rate-limiting enzymes/Regulation.

❑ Assess the ATP production (aerobic/anaerobic).

❑ Discuss importance of glycolysis.

 Glucose Oxidation
The pathways for oxidation of glucose are classified into :
I- The Major Pathways: for energy production.
A) Glycolysis, pyruvate is produced under aerobic condition
and lactate is produced under anaerobic condition.
B) Krebs’ cycle, pyruvate is converted to active acetate for
oxidation.
II- The Minor Pathways: for synthesis of other derivatives.
A) Hexose monophosphate pathway (HMP) for production of
pentoses and NADPH.
B) Uronic acid pathway for production of uronic acids.
 GLYCOLYSIS
(Embden-Meyerhof pathway)
• Glucose is the major source of energy for all cells.
• Glycolysis is derived from the Greek words (glykys = sweet
and lysis = splitting).
• Glycolysis means oxidation of glucose to give:
-Pyruvate in aerobic condition (in the presence of oxygen) or
-Lactate in anaerobic condition. (in the absence of oxygen)
• Site: Cytoplasm of all cells .
• Glycolysis is of physiological importance in:
1. Tissues with no mitochondria: mature RBCs, cornea and lens.
2. Tissues with few mitochondria: testis, leucocytes, medulla of
the kidney, retina, skin and gastrointestinal tract.
3. Tissues undergo frequent oxygen lack: skeletal muscles
especially during exercise.
4. In brain it is very essential as the brain is dependent in glucose
for energy.
Steps
There are 10 enzyme-catalyzed reactions occur in two phases:
• PHASE I (Energy utilization phase, reactions 1-5):
Glucose is phosphorylated and cleaved to yield 2 molecules of
glyceraldehyde-3-phosphate , phase I consumes 2 ATP.
• PHASE II (Energy recovery phase, reactions 6-10)
The 2 molecules of glyceraldehyde-3-phosphate are converted to
pyruvate and generation of 10 ATP (aerobic) or to lactate and
generation of 4ATP (anaerobic).
 Phase I
Step 1 Glucokinase or hexokinase (First ATP Utilization) Irreversible
A phosphoryl group is transferred from ATP to glucose to form
glucose 6-phosphate (G6P).
Step 2 Phosphohexose isomerase
Phosphohexose isomerase catalyzes the conversion of G6P to
F6P, the isomerization of an aldose to a ketose.
Step 3 Phosphofructokinase-1 (Second ATP utilization) Irreversible
PFK-1 phosphorylates fructose-6-phosphate gives fructose-1,6-
bisphosphate.
Step 4 Aldolase
Aldolase catalyzes cleavage of fructose-1,6-bisphosphate,this forms
two trioses:
- Glyceraldehyde-3-phosphate
- Dihydroxyacetone phosphate

Step 5 Triose Phosphate Isomerase

The isomerization of dihydroxyacetone phosphate this results in the
production of another molecules of glycerladehyde 3-phosphate.
Only glyceraldehyde-3-phosphate continues along the glycolytic
pathway.
 Phase II
Step 6 Glyceraldehyde-3-Phosphate Dehydrogenase
Conversion of glyceraldehyde-3-phosphate to1,3 bisphosphoglycerate.
During this reaction, NAD+ is reduced to NADH.
Step 7 Phosphoglycerate Kinase
Transfer of phosphoryl group from 1,3 bisphosphoglycerate to
ADP, forming ATP and 3 phosphoglycerate (Substrate level
phosphorylation).
Step 8 Phosphoglycerate mutase
3-phosphoglycerate is converted to 2-phosphoglycerate by
shifting the phosphate group from 3rd to 2nd carbon atom.
Step 9 Enolase
2-phosphoglycerate is converted to phosphoenol pyruvate by the
enzyme enolase (Dehydration reaction)
Step 10 Pyruvate Kinase (PK) Irreversible
Phosphoenol pyruvate (PEP) is dephosphorylated to pyruvate by
pyruvate kinase (substrate level phosphorylation).
Additional step in anaerobic condition
• Reduction of pyruvate to lactate by lactate dehydrogenase.
• The formation of lactate is the major fate for pyruvate in red
blood cells (no mitocondria)
Energy yield of glycolysis
In presence of oxygen:
• 2 ATP are consumed for conversion of glucose to fructose 1,6
bis P.
• 2 molecules of NADH are produced by G3-P dehydrogenase,
they are transported to the mitochondria where they are
oxidized by ETC and 6 molecules of ATP are produced.
• 4 ATP are produced by substrate level phosphorylation
- 2 by Phosphoglycerate kinase
- 2 by Pyruvate kinase
• Therefore, net gain of ATP in presence of oxygen is:
6+4 - 2= 8 ATP.
In absence of oxygen:
• 2 ATP are consumed for conversion of glucose to fructose 1,6
bis P.
• 2 molecules of NADH is not oxidized by ETC, it reacts with
pyruvate for regeneration of NAD+ and lactate.

• 4 ATP are produced by substrate level phosphorylation:

- 2 by Phosphoglycerate kinase
- 2 by Pyruvate kinase
• Therefore, net gain of ATP in absence of oxygen is: 4-2=2 ATP.
 Energy Yield per molecule of glucose in aerobic and anaerobic glycolysis
Step Enzymes catalyzed the Aerobic Anaerobic
reactions Source and Source and
No. of ATP No. of ATP

1 Hexokinase or -1 ATP -1 ATP

Glucokinase
3 Phosphofructokinase 1 -1 ATP -1 ATP

6 Glyceraldehyde-3- NADH 0
phosphate dehydrogenase + 6 ATP

7 Phosphoglycerate kinase substrate level substrate level

phosphorylation phosphorylation
+2 ATP +2 ATP
10 Pyruvate kinase substrate level substrate level
phosphorylation phosphorylation
+2 ATP +2 ATP
Net energy gain + 8 ATP +2 ATP
 Regulation of Glycolysis
All reactions of glycolysis are reversible except those catalyzed by:
• Glucokinase (GK) or hexokinase (HK) (Step 1)
• Phosphofructokinase-1 (PFK-1) (Step 3)
• Pyruvate kinase (PK) ) (Step10)
Glycolysis is regulated by factors which control the activity of
the key enzymes which catalyze the 3 irreversible reactions.
Regulating Steps of Glycolysis
 Regulation of glycolysis
A. Regulation according to energy requirements of cell:
• High levels of AMP (indicating decreased ATP availability)
activates glycolysis.
• High levels of ATP (indicating decreased utilization of ATP)
inhibits glycolysis.
B. Regulation by hormones:
Insulin/glucagon ratio is the main hormonal regulator of
glucose utilization, it increases during carbohydrate feeding and
decreases during fasting or glucose deprivation.
- Insulin, it is secreted by the pancreas after feeding of carbs in
response to high blood glucose level (hyperglycemia) activates
glycolytic key enzymes
• So the cells take up glucose faster, more ATP is formed,
glycogen and fatty-acid production increases.
- Glucagon, it is secreted by the pancreas in case of glucose
deficiency in response to low blood glucose level (hypoglycemia),
it inactivates glycolytic key enzymes.
• So the stored glycogen is converted to glucose.
Importance of Glycolysis:
• The only pathway that is taking place in all the cells of the body.
• Pyruvate provides the mitochondrial oxaloacetate which is the
initiator of the Krebs' cycle. It is also converted to active acetate
used in Krebs' cycle to produce more energy.
• Dihydroxyacetone phosphate can give glycerol 3-phosphate
which is utilized for synthesis of triacylglycerols and
phospholipids.
• The intermediates of glycolytic pathway provides carbon
skeletons for synthesis of non- essential amino acids ( as
serine from 3 phosphoglycerate and alanine from pyruvate )
• Energy production: glycolysis liberates only a small part of
energy from glucose, however:
- It is very important during severe muscular exercise, when
muscle tissues lack enough oxygen, anaerobic glycolysis
forms the major source of energy for muscles
- It provides all energy required by the RBCs. (no mitochondria).
Fate of pyruvate
1-Conversion to lactate under anaerobic conditions in cytosol

2-Conversion to active acetate (acetyl CoA) in mitochondria

3- Conversion to oxaloacetate in mitochondria

Thank You