Glycolysis is the metabolic pathway that converts glucose C₆H₁₂O₆, into pyruvate, CH₃COCOO⁻, and a hydrogen ion, H⁺. The free energy released in this process is used to form the high-energy molecules ATP and NADH. Glycolysis is a sequence of ten enzyme-catalyzed reactions.
Glycolysis is an oxygen-independent metabolic pathway. The wide occurrence of glycolysis indicates that it is an ancient metabolic pathway. Indeed, the reactions that constitute glycolysis and its parallel pathway, the pentose phosphate pathway, occur metal-catalyzed under the oxygen-free conditions of the Archean oceans, also in the absence of enzymes.
3. 1. GLYCOLYSIS
INTRODUCTION:
* Glycolysis is derived from greek word (glycose-glucose, lysis-
breakdown).
* During this process one molecules of glucose is degraded into
two molecules of pyruvate.
* Free energy is released in this process and is stored as two
molecules of “ATP” and two molecules of NADH.
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4. 2. HISTORY:
• Glycolysis was the very 1st biochemistry studied and it is the 1st metabolic
pathway discovered.
• Louis pasture (1854-1864): observed that fermentation is caused by micro-
organisms and also found that aerobic growth requires less glucose than
anaerobic condition.
• Buchner (1897): found that reaction of glycolysis can be carried out in a cell-free
yeast extract.
• Harden and young (1905): found that (1). Inorganic phosphate is required
fermentation.
(2). Yeast extract could be separated in small molecular weight essential coenzymes
and bigger molecules called zymase.
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• There is 60% of ingested food consist of polysaccharide carbohydrates,
while the disaccharide carbohydrates like sucrose and lactose are important
in the diet of infants.
• The end product of carbohydrate digestion is mainly glucose, fructose and
galactose.
• These simple sugars are absorbed in the intestine and are carried to the liver
through the blood stream. Here they are transferred into glycogen through
glucose-6-phosphate.
• The glycogen is stored in the liver.
• The carbohydrate metabolism or digestion of carbohydrate is takes by two
steps:
1. Catabolism
2. Anabolism
6. 1. Catabolism:
* In catabolism degradation of complex organic
molecules into simpler molecules.
* In this process energy is released.
2. Anabolism:
* Anabolism is the process of biosynthesis in
which complex molecules are produced from simpler
molecules.
* In this process energy is required.
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7. Glycolysis: ( Embden-meyerhof-parnas method/pathway)
* Glycolysis is the breakdown of glucose upto the formation of
pyruvic acid. Each glucose molecules forms two molecules of pyruvic acid.
* The breakdown of glucose is takes place in a series of steps, each
stepwise reaction is catalyzed by a specific enzyme.
* Glycolysis may be divided into two phases :
1. Preparatory phase.
2. Oxidative phase.
1. Preparatory phase :-
* The 1st four (1-4) steps in glycolysis represents the
preparatory phase.
* In this phase breakdown of glucose and low energy
phosphorylation occurs and I is expended.
2. Oxidative phase :-
* The end (5-9) steps in glycolysis represents the
oxidative phase.
* In this phase high-energy phosphate bonds are formed
and the energy is stored.
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11. Steps involved in Glycolysis :-
• It is the first step in the breakdown of carbohydrates.
• The glucose is stable compound so, it normally resist the
breakdown.
• The activation of glucose molecule takes place by a
reaction called oxidative phosphorylation.
• A phosphate group is attached to glucose by a low energy
phosphate bond ( -p ), and glucose-6-phosphate is formed.
• The reaction is facilitated by an enzyme called
Hexokinase with mg2+ as an activator.
• The phosphate group is derived from ATP which
breakdown to ADP.
example:-
* The hormones insulin and estrogen
promote phosphorylation of blood glucose to glucose-6-
phosphate.
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12. 2. ISOMERISATION:-
• Glucose-6-phosphate undergoes internal molecular
rearrangement to form Fructose-6-phosphate.
• The catalytic enzyme is Phosphoglucoisomerase.
• No changes takes place in the low energy value of the
phosphate bond.
3. SECOND PHOSPHORYLATION :-
• Fructose-6-phosphate undergoes phosphorylation to
form fructose-1,6-diphosphate.
• The catalytic enzyme is phosphofructokinase.
• The phosphate group is derived from ATP which
breaks down to ADP.
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13. 4. CLEAVAGE:-
• Fructose-1,6-diphosphate splits into two halves between
carbon atom 3 and 4 under the action of enzyme Aldolase.
• The two halves phosphates, each contain three carbon
atoms, but are not identical.
• The one half is dihyroxyacetone phosphate (DHAP )
and the other is 3-phosphoglyceraldehyde.
• These molecules undergoes isomerization and become
identical 3-phosphoglyceraldehyde (PGAL ) molecules.
• The catalyzing enzyme is Triosephosphate isomerase.
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14. 5. PHOSPHORYLATION AND OXIDATIVE DEHYDROGENATION :-
• The phosphoglyceraldehyde ( PGAL ) undergoes
simultaneous phosphorylation and oxidative dehydrogenation.
• The PGAL molecule has a phosphate group attached to the
one end by a low energy bond ( -p ).
• During phosphorylation, under the catalyzing action of
enzyme phosphotriose dehydrogenase, a second phosphate
group is added to the other end.
• The phosphorylating agent which provides the phosphate
group is phosphoric acid.
• Oxidative dehydrogenation takes place simultaneously. Two
atoms of hydrogen are removed and are accepted by NAD+
(nicotinamide adenine dinucleotide), which is converted into
NADH+H+ .
• The newly added phosphate group acquires a high energy
phosphate bond ( ~ P ). The end product is 1, 3-
diphosphoglyceric acid, an energy rich compound is formed. .
15. 6. ATP GENERATION :-
• 1, 3-diphosphoglyceric acid now transfer its phosphate with
high energy bond to ADP, 3-phosphoglyceric acid ( PGAL ).
• The catalytic enzyme is phosphoglyceryl kinase.
• ADP acquires the high energy bond phosphate and becomes
ATP,
7. ISOMERIZATION :-
• The 3-phosphoglyceric acid molecules undergoes internal
rearrangement and becomes 2-phosphoglyceric acid.
• The catalyzing enzyme is phosphoglyceromutase.
8. DEHYDRATION:-
• The 2-phosphoglyceric acid molecules loses hydrogen and
oxygen in the form of water ( dehydration ), to form phosphoenol
pyruvic acid.
• The step is catalyzed by an enzyme Enolase.
16. 9. ATP GENERATION :-
• The phosphoenol pyruvic acid molecules transfers its
high energy phosphate bond to ADP, which is converted
into ATP, and pyruvic acid is formed.
• The reaction is catalyzed by an enzyme called Pyruvate
kinase.
• It should be noted that two molecules of pyruvic acid are
formed per molecules of glucose metabolished.
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4. BIOLOGICAL SIGNIFICANCE:-
* In the absence of oxygen pyruvic acid is converted into either ethyl
alcohol or lactic acid.
* Pyruvic and lactic acids may be returned to the liver where they can be
resynthesized to form glucose or glycogen by reverse anaerobic glycolysis.
* Lactic and pyruvic acids may also be broken down in the liver to yield
carbon dioxide and water through kreb’s cycle .
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5. References:-
I. Lehninger’s Principle of Biochemistry (5th) Edition - David L.
Nelson & Michael M. Cox.
II. Fundamentals of Biochemistry – J.L.JAIN 2005 S. CHAND &
COMPANY LTD. RAM NAGAR, NEW DELHI-110 055
III. https://en.wikipedia.org/wiki/Glycolysis