This document provides an overview of glycolysis. It begins by defining glycolysis as the pathway that converts glucose to pyruvate with production of ATP. It then discusses the specific reactions of glycolysis in three phases: the energy investment phase where ATP is used to phosphorylate glucose, the splitting phase where a 6-carbon molecule splits into two 3-carbon molecules, and the energy generation phase where ATP is produced. Key points include that glycolysis occurs in the cytoplasm and produces 2 ATP net per glucose molecule under anaerobic conditions, or up to 8 ATP net per glucose under aerobic conditions when the NADH produced is further oxidized in the mitochondria. The document also notes some regulation and applications of glycolysis.
3. Introduction
• GLYCOLYSIS is the sequence of 10 enzyme-catalyzed
reactions that converts glucose into pyruvate with
simultaneous production on of ATP.
• In this oxidative process, 1mol of glucose is partially
oxidised to 2 moles of pyruvate.
4. • This major pathway of glucose metabolism occurs in
the cytosol of all cell.
• This unique pathway occurs aerobically as well as
anaerobically & doesn’t involve molecular oxygen.
Cont.….
6. • Glycolysis is derived from the Greek words (glycose—
sweet or sugar; lysis—dissolution).
• It is a universal pathway in the living cells.
• The complete pathway of glycolysis was elucidated in 1940.
Cont.….
7. • This pathway is often referred to as Embden-Meyerhof
Parnas pathway (E.M. P. pathway) in honour of the
three biochemists Gustav Embden, Otto Meyerhof,
and Jakub Karol Parnas who made a major
contribution to the knowledge of glycolysis.
Cont.….
8. Cont…
• Glycolysis splits a 6-carbon sugar, glucose, into two
molecules of 3-carbon pyruvate in a series of steps,
each catalyzed by a particular enzyme.
• Glycolysis takes place in the cytoplasm (cytosol) of
all living cells, not in mitochondria, and does not
require the presence of oxygen. Therefore,
glycolysis is also known as cytoplasmic respiration.
9. Definition
Glycolysis is defined as the sequence of reactions
converting glucose (or glycogen) to pyruvate or
lactate, with the production of
ATP 16
10. Salient features
• Takes place in all cells of the body.
• Enzymes present in “cytosomal fraction” of the cell.
• Glycolysis occurs in the absence of oxygen
(anaerobic) or in the presence of oxygen (aerobic).
• Lactate – end product – anaerobic condition.
• Pyruvate(finally oxidized to CO2 & H2O) – end product
of aerobic condition.
• Glycolysis is a major pathway for ATP synthesis in tissues
lacking mitochondria, e.g. erythrocytes, cornea, lens etc.
11. Cont.….
• Glycolysis is very essential for brain which is dependent
on glucose for energy.
• The glucose in brain has to undergo glycolysis before it is
oxidized to CO2 and H2O.
• Glycolysis (anaerobic) may be summarized by the net
reaction
Glucose + 2ADP + 2Pi (Inorganic Phosphate)
2 Lactate + 2ATP
12. Cont.….
• Glycolysis is a central metabolic pathway with many
of its intermediates providing branch point to other
pathways. Thus, the intermediates of glycolysis are
useful for the synthesis of amino acids and fat.
• Reversal of glycolysis along with the alternate
arrangements at the irreversible steps, will result in the
synthesis of glucose (gluconeogenesis).
13. Reactions of Glycolysis
A. Energy Investment phase (or) priming phase
B. Splitting phase
C. Energy generation phase
14. A. Energy Investment phase (or) priming
phase
1. Glucose is phosphorylated to glucose 6-phosphate by
hexokinase or glucokinase (both are isoenzymes).
• This is an irreversible reaction, dependent on ATP and
Mg2+.
• The enzyme hexokinase is present in almost all the
tissues.
15. Cont….
• It catalyses the phosphorylation of various hexoses
(fructose, mannose etc.), has low Km (Michaelis
constant) for substrates (about 0.1 mM) and is inhibited
by glucose 6-phosphate.
• Glucokinase present in liver, catalyses the
phosphorylation of only glucose, has high Km for glucose
(10 mM) and is not inhibited by glucose 6-phosphate.
16. Cont…..
• Due to high affinity (low Km), glucose is utilized by
hexokinase even at low concentration, whereas glucokinase
acts only at higher levels of glucose i.e., after a meal when
blood glucose concentration is above 100 mg/dl.
• Glucose 6-phosphate is impermeable to the cell membrane.
• It is a central molecule with a variety of metabolic fates—
glycolysis, glycogenesis, gluconeogenesis and pentose
phosphate pathway.
17. Cont…..
2. Glucose 6-phosphate undergoes isomerization to give
fructose 6-phosphate in the presence of the enzyme
phosphohexose isomerase and Mg2+.
3. Fructose 6-phosphate is phosphorylated to fructose
1,6-bisphosphate by phosphofructokinase (PFK). This is
an irreversible and a regulatory step in glycolysis.
18. 2) Splitting phase
4. The six carbon fructose 1,6- bisphosphate is split
(hence the name glycolysis) to two three-carbon
compounds, glyceraldehyde 3-phosphate and
dihydroxyacetone phosphate by the enzyme aldolase
(fructose 1,6- bisphosphate aldolase).
19. Cont…..
5. The enzyme phosphotriose isomerase catalyses the
reversible interconversion of glyceraldehyde 3-
phosphate and dihydroxyacetone phosphate. Thus, two
molecules of glyceraldehyde 3-phosphate are obtained
from one molecule of glucose.
20. 3) Energy generation phase
6. Glyceraldehyde 3-phosphate dehydrogenase converts
glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate.
This step is important as it is involved in the formation of
NADH + H+ and a high energy compound 1,3-
bisphosphoglycerate.
Lodoacetate and arsenate inhibit the enzyme glyceraldehyde
3-phosphate dehydrogenase.
In aerobic condition, NADH passes through the electron
transport chain and 6 ATP (2 X 3 ATP) are synthesized by
oxidative phosphorylation
21. Cont…..
7. The enzyme phosphoglycerate kinase acts on 1,3-
bisphosphoglycerate resulting in the synthesis of ATP
and formation of 3-phosphoglycerate.
This step is a good example of substrate level
phosphorylation, since ATP is synthesized from the
substrate without the involvement of electron transport
chain.
Phosphoglycerate kinase reaction is reversible, a rare
example among the kinase reactions.
22. Cont…..
8. 3-Phosphoglycerate is converted to 2-
phosphoglycerate by phosphoglycerate mutase.
This is an isomerization reaction.
23. Cont…..
9. The high energy compound phosphoenol pyruvate is
generated from 2-phosphoglycerate by the enzyme
enolase.
This enzyme requires Mg2+ or Mn2+ and is inhibited by
fluoride.
For blood glucose estimation in the laboratory, fluoride is
added to the blood to prevent glycolysis by the cells, so that
blood glucose is correctly estimated.
24. Cont…..
(Fluoride combines with Mg2+ and phosphate to form a
complex that binds with active site of enolase and blocks
access of substrate. Thus, fluoride is an unusual
competitive inhibitor).
25. Cont…..
10. The enzyme pyruvate kinase catalyses the transfer
of high energy phosphate from phosphoenol pyruvate to
ADP, leading to the formation of ATP. This step also is a
substrate level phosphorylation. This reaction is
irreversible
29. Energy production of glycolysis
ATP production = ATP produced – ATP utilized
ATP production ATP
produced
ATP utilized
In absence
of oxygen
(anaerobic
glycolysis)
4 ATP
(Substrate level
phosphorylation)
2 ATP from 1, 3 DPG
2 ATP from
phosphoenol pyruvate
2 ATP
from
glucose to
glucose 6-
p.
From
fructose -
6-p to
fructose
1,6 p.
2 ATP
30. Cont.…..
ATP production ATP
produced
ATP utilized
In presence
of oxygen
(aerobic
glycolysis)
4 ATP
(Substrate level
phosphorylation)
2 ATP from 1, 3 BPG
2 ATP from
phosphoenol pyruvate
+ 4ATP or 6 ATP
(from oxidation of 2
NADH + H in
mitochondria).
2 ATP
from
glucose to
glucose 6-
p.
From
fructose -
6-p to
fructose
1,6 p.
8 ATP / 6
ATP
(Pyruvate
dehydrogen
ase
2NADH,ET
C, Oxidative
phosphoryla
tion)