GLYCOLYSIS

INTRODUCTION:

 Glycolysis is the sequence of reactions that

metabolizes one molecule of glucose to two
molecules of pyruvate with the net production of
two molecules of ATP.
 Glycolysis, the major pathway for glucose
metabolism, occurs in the cytosol of all cells.
 In aerobic glycolysis the end product is
pyruvate.
 In anaerobic glycolysis pyruvate is converted to
lactate.
Glycolysis: General Functions

Provide ATP energy

Generate intermediates for other pathways

 G-6-PHexose monophosphate pathway(goes
off to make the ribose for nucleotides)&

Glycogen synthesis
 F-6-P amino sugars, glycolipids and
glycoproteins
 Pyruvate dehydrogenase Acetyl CoA

(Fatty acid synthesis and Krebs’ Cycle)

Glycerol-3phosphate/DHAP (TG synthesis)

3PG (serine) – Pyruvate (alanine)

 Tissues That Function Under Hypoxic
Circumstances Tend to Produce Lactate
 In skeletal muscle (e.g. white fibers) the need
for ATP formation may exceed the rate at
which oxygen can be taken up and utilized.
 Glycolysis in erythrocytes, even under
aerobic conditions, terminates in lactate,
because erythrocytes lack mitochondria.
 Other tissues that normally derive much of
their energy from glycolysis and produce
lactate include brain, gastrointestinal
tract, renal medulla, retina and skin.
 The liver, kidneys, and heart usually take
up lactate and oxidize it but will produce it
under hypoxic conditions.
 In erythrocytes, the first site in glycolysis

for generation of ATP may be bypassed,

leading to the formation of 2,3-

bisphosphoglycerate, which is important in

decreasing the affinity of hemoglobin for

O2.
Bisphosphoglycerate pathway in-2,3
.erythrocytes
 THE PATHWAY OF GLYCOLYSIS

Stage 1: Conversion of glucose into fructose

1,6-bisphosphate.
 It consists of three steps: a phosphorylation,
an isomerization, and a second
phosphorylation reaction.
 Stage 2:

Cleavage of the fructose 1,6-bisphosphate

into two three-carbon fragments.
 Stage 3 :

ATP is produced when the three-carbon

fragments are oxidized to pyruvate.
 6 CH 2 O H 6 CH O PO 2 
2 3
ATP ADP
5 O 5 O
H H H H
H H
4 1 4 H 1
OH H OH
M g 2+
OH OH OH OH
3 2 3 2
H OH H ex ok inase H OH
glucose glucose -6 -ph osp hate

1. Hexokinase or glucokinase catalyzes:

Glucose + ATP  glucose-6-P + ADP
Requires Mg++ as cofactor.
 GLUKOKINASE HEXOKINASE
Site -1 Liver only All tissue cells

Affinity to glucose .2 Low affinity (high km) high affinity (low km)

substrate .3 Glucose only Glucose, galactose and

fructose
Effect of insulin .4 Induces synthesis of No effect
glucokinase
Effect of glucose 6.5 No effect Allosterically inhibits
hexokinase
phosphate
function .6 Act in liver after meals .it It phosphorylate glucose
removes glucose coming in inside the body cells .this
portal circulation ,converting makes glucose concentration
it into G.6.P more in blood than inside the
cells. This leads to continuous
supply of glucose for the
tissues even in the presence of
low blood glucose
concentration
 6 CH O PO 2 
2 3
6 CH 2
5 O 2 O PO 3 1 CH 2 O H
H H O
H
4 H 1 5 H HO 2
OH
OH OH H 4 3 OH
3 2
OH H
H OH
P h o s p h o g lu c o s e Is o m e ra s e
g lu c o s e -6 -p h o s p h a te fru c to s e -6 -p h o s p h a te

2. Phosphohexose Isomerase catalyzes:

glucose-6-P (aldose)  fructose-6-P (ketose)
 P h o s p h o fru c to k in a s e
2 2
6 CH
2 O PO 3 1 CH 2 O H 6 CH
2 O PO 3 1 CH 2 O PO 3 2 
O ATP ADP O
5 H HO 2 5 H HO 2

H 4 3 OH M g2+ H 4 3 OH
OH H OH H
fru c to s e -6 -p h o s p h a te f r u c t o s e - 1 ,6 - b i s p h o s p h a t e

3. Phosphofructokinase catalyzes:
fructose-6-P + ATP  fructose-1,6-bisP + ADP
The Phosphofructokinase reaction is the rate-limiting step
of Glycolysis.
The enzyme is highly regulated, as will be discussed later.
 2
1 CH 2 O PO 3

2C O
H O
2
HO 3 C H A ld o la se 3
CH 2 O PO 3 1C

H 4C OH 2C O + H 2C O H
2
H C OH 1 CH 2 O H 3 CH 2 O PO 3
5
2 d ih y d ro x y a c e to n e g ly c e ra ld e h y d e -3 -
6 CH 2 O PO 3
p h o sp h a te p h o sp h a te
fru c to se -1 ,6 -
b isp h o sp h a te
T rio se p h o sp h a te Iso m e ra se

4. Aldolase catalyzes: fructose-1,6-bisphosphate 

dihydroxyacetone-P + glyceraldehyde-3-P
 2
1 CH 2 O PO 3

2C O
H O
2
HO 3 C H A ld o la se 3
CH 2 O PO 3 1C

H 4C OH 2C O + H 2C O H
2
H C OH 1 CH 2 O H 3 CH 2 O PO 3
5
2 d ih y d ro x y a c e to n e g ly c e ra ld e h y d e -3 -
6 CH 2 O PO 3
p h o sp h a te p h o sp h a te
fru c to se -1 ,6 -
b isp h o sp h a te
T rio se p h o sp h a te Iso m e ra se

5. Triose Phosphate Isomerase catalyzes:

dihydroxyacetone-P  glyceraldehyde-3-P
Glycolysis continues from glyceraldehyde-3-P.
 G ly c e ra ld e h y d e -3 -p h o s p h a te
D e h y d ro g e n a se
2
H O + H+ O O PO 3
+
1 C NAD NADH 1 C
+ P i
H C OH H C OH
2 2
2 2
3 CH 2O PO 3 3 CH 2O PO 3

g ly c e ra ld e h y d e - 1 ,3 -b is p h o s p h o -
3 -p h o s p h a te g ly c e ra te

6. Glyceraldehyde-3-phosphate Dehydrogenase
catalyzes:
glyceraldehyde-3-P + NAD+ + Pi 
1,3-bisphosphoglycerate + NADH + H+
 P h o s p h o g ly c e ra te K in a s e
2 
O O PO 3 ADP ATP O O
1C 1
C
H 2
C OH H 2
C OH
2+
2 Mg 2
3 CH 2 O PO 3 3 CH 2 O PO 3

1 ,3 - b i s p h o s p h o - 3 -p h o s p h o g ly c e ra te
g ly c e ra te

7. Phosphoglycerate Kinase catalyzes:

1,3-bisphosphoglycerate + ADP 
3-phosphoglycerate + ATP
 P h o s p h o g ly c e r a te M u ta s e
O O O O
1
C 1
C
2
H 2C O H H 2 C O PO 3
2
3 CH 2 O PO 3 3 CH 2 O H
3 -p h o s p h o g ly c e r a te 2 -p h o s p h o g ly c e r a te

8. Phosphoglycerate Mutase catalyzes:

3-phosphoglycerate  2-phosphoglycerate

Phosphate is shifted from the OH on C3 to the OH on C2.

 E n o la s e
O  H 
O  OH O
O O O
C C 1
C
1
H 2 C O P O 32 C O P O 32 2C O P O 32

3 C H 2O H C H 2O H 3CH2
2 -p h o s p h o g ly c e ra te e n o la te in te r m e d ia te p h o s p h o e n o lp y r u v a te

9. Enolase catalyzes:
2-phosphoglycerate  phosphoenolpyruvate + H2O
This dehydration reaction is Mg++-dependent.
 P y ru v a te K in a s e
O O O O
ADP ATP
1
C 1
C

2
C O PO 3 2  2
C O

3 CH 2 3 CH 3
p h o s p h o e n o lp y ru v a te p y ru v a te

10. Pyruvate Kinase catalyzes:

phosphoenolpyruvate + ADP  pyruvate + ATP
 glucose Glycolysis
ATP
Hexokinase
ADP
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
ATP
Phosphofructokinase
ADP
fructose-1,6-bisphosphate
Aldolase

glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
Glycolysis continued
 glyceraldehyde-3-phosphate
NAD+ + Pi Glyceraldehyde-3-phosphate
NADH + H+ Dehydrogenase
1,3-bisphosphoglycerate
Glycolysis ADP
continued. Phosphoglycerate Kinase
ATP
Recall that 3-phosphoglycerate
there are 2 Phosphoglycerate Mutase
GAP per 2-phosphoglycerate
glucose.
H2O Enolase
phosphoenolpyruvate
ADP
Pyruvate Kinase
ATP
pyruvate
 2 ATP expended
 4 ATP produced (2 from each of two 3C fragments
from glucose)
 Net production of 2 ATP per glucose.

Glycolysis - total pathway, omitting H+:

glucose + 2 NAD+ + 2 ADP + 2 Pi 
2 pyruvate + 2 NADH + 2 ATP
Under aerobic conditions

NADH produced in Glycolysis & Krebs Cycle is

re oxidized via the respiratory chain, with
production of 3ATP
 pyruvate is taken up into mitochondria and
after conversion to acetyl-CoA is oxidized to
CO2 by the citric acid cycle.
 Under Anaerobic condition
The reoxidation of NADH via lactate formation
allows glycolysis to proceed in the absence of
oxygen by regenerating sufficient NAD+ for
another cycle of the reaction catalyzed by
glyceraldehyde-3-phosphate dehydrogenase
 L a c ta te D e h y d ro g e n a s e
O O O O
C NADH + H+ NAD+ C
C O HC OH
CH 3 CH 3
p y ru v a te la c ta te
 Fate of lactate
1. Glucose formation by (cori cycle)
2. Conversion into pyruvate, if oxygen gets
available.
3. May be accumulated in muscles causing muscle
fatigue.
4. Lactate may be excreted in urine
 P y ru v a te A lc o h o l
D e c a rb o x y la s e D e h y d ro g e n a se
O 
O
CO H NADH + H+ NAD +
H
C 2 O
C O C H C OH

CH CH 3 CH 3
3
p y ru v a te a c e ta ld e h y d e e th a n o l

Fermentation (conversion of glucose into ethanol by yeast

enzymes)
Glucose by glycolysis give pyruvate then to ethanol NADH
is converted to NAD+ in the reaction catalyzed by Alcohol
Dehydrogenase.
 Enzymes of Glycolysis

Hexokinase or glucokinase
Phosphohexose Isomerase
Phosphofructokinase
Aldolase
Triosephosphate Isomerase
Glyceraldehyde-3-P Dehydrogenase
& Phosphoglycerate Kinase
Phosphoglycerate Mutase
Enolase
Pyruvate Kinase