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Glycolysis

PABZA

Assoc. Prof. Dr. Atif Amin Baig ,


Faculty of Medical Sciences,
University Sultan Zainal Abidin.
atifamin@unisza.edu.my
Recalls
1. What is a difference between digestion and absorption of carbohydrates?

2. Overview of the anatomical and histological associations of eliminatory canal.

3. Sources of carbohydrates in diet.

4. Mastication and functions of deciduous and permanent teeth

5. Stages of carbohydrate digestion

6. Stages of carbohydrate resorption

7. Gastric secretions

8. Integrated metabolic pathways for carbohydrates (CLO)


Learning Outcomes
1. Integrated metabolic pathways for carbohydrates (CLO), an overview

2. What is glycolysis

3. Importance of glycolysis in carbohydrate metabolism

4. Importance of glycolysis in anaerobic conditions

5. Aerobic Vs anaerobic glycolysis

6. Reactions and Phases of glycolysis

7. Steps of glycolysis

8. ATP Yield per mole of glucose?

9. Energy profiles during glycolysis

10. Integration of carbohydrate molecules with glycolysis and energy yield


Integration of metabolic pathways
(overview)
Glycolysis
• Definition

Glycolysis is a catabolic pathway in the cytoplasm that is found in


almost all organisms—irrespective of whether they live
aerobically or anaerobically.
Site of glycolysis
• Cytosol in all organisms
• Glycosome (1868)
Summary of glycolysis
The balance of glycolysis is simple: glucose is broken down into
two molecules of pyruvate, and in addition two molecules of ATP
and two of NADH+H+ are formed.
Need of glycolysis
Glucose occupies a central position in the metabolism of plants,
animals and many micro-organisms.

Extracellular matrix and cell Glycogen, Starch,


Wall polysaccharides Sucrose

Synthesis of Storage
Structural polymers

Glucose
Oxidation via pentose Oxidation via
phosphate pathway Glycolysis

Ribose 5-phosphate Pyruvate


Aerobic Vs Anaerobic glycolysis

In the presence of oxygen, lactate


pyruvate and or ethanol have to be formed
NADH+H+ reach the in the cytoplasm
mitochondria, where from pyruvate and NADH+H+,
they undergo further in order to regenerate
transformation NAD+ so that glycolysis can
continue

In the anaerobic state, glycolysis is the only means of obtaining ATP that animal cells have.
Reactions of glycolysis
• A total of 10 individual steps
• Divided into 2 parts

1. Energy Investment
2. Energy Generation
Phases of glycolysis
• Phase 1 (Energy Investment)
o First 5 reactions
• Phase 2 (Energy generation)
o Last 5 reactions
Reactions of Glycolysis
Phase 1: Energy Investment
• Reaction 1: Phosphorylation
• Reaction 2: Isomerization
• Reaction 3: Phosphorylation
• Reaction 4: Cleavage
• Reaction 5: Isomerization
Reactions of Glycolysis
Phase 2: Energy Generation
• Reaction 6: Oxidation and
Phosphorylation
• Reaction 7: Substrate level
Phosphorylation
• Reaction 8: Isomerization
• Reaction 9: Dehydration
• Reaction 10: Substrate level
Phosphorylation
Step 1
Glucose, which is taken up by
animal cells from the blood
and other sources, is first
phosphorylated to glucose 6-
phosphate, with ATP being
consumed. The glucose 6-
phosphate is not capable of
leaving the cell.
Step 2
In the next step,
glucose 6-phosphate is
isomerized into
fructose 6-phosphate.
Step 3
Using ATP again, another
phosphorylation
takes place, giving rise to
fructose 1,6-
bisphosphate.
Phosphofructokinase is the
most important key enzyme in
glycolysis
Step 4
Fructose 1,6-bisphosphate is broken
down by aldolase into the C3
compounds glyceraldehyde
3-phosphate (also known as glyceral
3-phosphate) and glycerone 3-
phosphate
(dihydroxyacetone 3-phosphate).
Step 5
The latter two
products are
placed in
fast equilibrium by
triosephosphate
isomerase.
Step 6
Glyceraldehyde 3-phosphate is now
oxidized by glyceraldehyde-3-
phosphate dehydrogenase, with
NADH+H+ being formed. In this
reaction, inorganic phosphate is
taken up into the molecule
(substrate-levelphosphorylation)
and 1,3-bisphosphoglycerate
is produced. This intermediate
contains a mixed acid–anhydride
bond, the phosphate part of which
is at a high chemical potential.
Step 7
Catalyzed by
phosphoglycerate kinase,
this phosphate residue is
transferred to ADP,
producing 3-
phosphoglycerate and
ATP. The
ATP balance is thus once
again in equilibrium.
Step 8
As a result of shifting of the
remaining
phosphate residue within the
molecule, the
isomer 2-phosphoglycerate is
formed.
Step 9
Elimination of water from
2-phosphoglycerate
produces the phosphate
ester of the
enol form of pyruvate—
phosphoenolpyruvate
(PEP). This reaction also
raises the second
phosphate residue to a
high potential.
Step 10
In the last step, pyruvate kinase transfers
this residue to ADP. The remaining enol
pyruvate is immediately rearranged into
pyruvate, which is much more stable. Along
with step [7] and the thiokinase reaction in
the tricarboxylic acid cycle (see p. 136), the
pyruvate kinase reaction is one of the three
reactions in animal metabolism that are able
to produce ATP independently of the respiratory
chain.
ATP/mole of glucose?

In glycolysis, two molecules


of ATP are initially
used for activation ([1], [3]).
Later, two
ATPs are formed per C3
fragment. Overall,
therefore, there is a small net
gain of 2 mol
ATP per mol of glucose.

Steps 1 and 3 = - 2ATP


Steps 7 and 10 = + 4 ATP
Net "visible" ATP produced = 2.
Energy Profiles
• The energy balance of
metabolic pathways depends
not only on the standard
changes in enthalpy ΔG0, but
also on the concentrations of
the metabolites).
• Fig. C shows the actual
enthalpy changes ΔG for the
individual steps of glycolysis
in erythrocytes.

As can be seen, only three reactions ([1],


[3], and [10]), are associated with large
changes in free enthalpy. In these cases,
the equilibrium lies well on the side of
the products. All of the other steps are
freely reversible.
Summary of Reactions
Integration of carbohydrates with
Glycolysis
Thank you

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