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Glycolysis
By SIR Moazzam Ali Shahid
Metabolism The complex of physical and chemical
processes occurring within a living cell or organism that are necessary for the maintenance of life.
In metabolism some substances are broken down to yield energy for vital processes while other substances, necessary for life, are synthesized.
1. Occurs in the cytosol outside the mitochondria.
2. The breakdown of glucose to 2 pyruvate molecules.
Glycolysis:
1. Glycolysis begins with addition of 2 phosphate groups, activating glucose to react.
2. Two separate reactions use 2 ATP.
3. Glucose, a C6 molecule, splits into two C3 molecules, each with a phosphate group.
Energy Investment Steps
Substrate Level Phosphorylation
C. Energy Harvesting Steps
Steps In Glycolysis
1. Hexokinase
Glucose + ATP glucose-6-P + ADP
H O
OH
H
OHH
OH
CH2OH
H
OH
H H O
OH
H
OHH
OH
CH2OPO32
H
OH
H
23
4
5
6
1 1
6
5
4
3 2
ATP ADP
Mg2+
glucose glucose-6-phosphate
Hexokinase
2. Phosphoglucose Isomerase catalyzes:
glucose-6-P (aldose) fructose-6-P (ketose)
H O
O H
H
O HH
O H
CH 2 O PO 32
H
O H
H
1
6
5
4
3 2
CH 2 O PO 32
O H
CH 2 O H
H
O H H
H HO
O6
5
4 3
2
1
g lu c o s e - 6 - p h o s p h a te f r u c to s e - 6 - p h o s p h a te P h o s p h o g lu c o s e Is o m e r a s e
3. Phosphofructokinase catalyzes:
Fructose-6-P + ATP fructose-1,6-bisP + ADP
CH 2 O PO 32
O H
CH 2 O H
H
O H H
H HO
O6
5
4 3
2
1 CH 2 O PO 32
O H
CH 2 O PO 32
H
O H H
H HO
O6
5
4 3
2
1
A T P A D P
M g 2 +
f r u c t o s e - 6 - p h o s p h a t e f r u c t o s e - 1 , 6 - b i s p h o s p h a t e
P h o s p h o f r u c t o k i n a s e
4. Aldolase catalyzes: fructose-1,6-bisphosphate dihydroxyacetone-P + glyceraldehyde-3-P.
6
5
4
3
2
1 CH 2 O PO 32
C
C
C
C
CH 2 O PO 32
O
HO H
H O H
H O H
3
2
1
CH 2 O PO 32
C
CH 2 O H
O
C
C
CH 2 O PO 32
H O
H O H+
1
2
3
f ru c to s e -1 ,6 - b is p h o s p h a te
A ld o la s e
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 - p h o s p h a te p h o s p h a te
T rio s e p h o s p h a te Is o m e ra s e
5. Triose Phosphate Isomerase (TIM) catalyzes:
dihydroxyacetone-P glyceraldehyde-3-P
6
5
4
3
2
1 CH 2 O PO 32
C
C
C
C
CH 2 O PO 32
O
HO H
H O H
H O H
3
2
1
CH 2 O PO 32
C
CH 2 O H
O
C
C
CH 2 O PO 32
H O
H O H+
1
2
3
f ru c to s e -1 ,6 - b is p h o s p h a te
A ld o la s e
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 - p h o s p h a te p h o s p h a te
T rio s e p h o s p h a te Is o m e ra s e
C
C
CH 2 O H
O O
H O PO 32
2
3
1C
C
CH 2 O PO 32
O O
H O H2
3
1
3 - p h o s p h o g l y c e r a t e 2 - p h o s p h o g l y c e r a t e
P h o s p h o g l y c e r a t e M u t a s e
C
C
CH2OPO32
O O
H OPO32
2
3
1
2,3-bisphosphoglycerate
An active site histidine side-chain participates in Pi transfer, by donating & accepting phosphate.
The process involves a 2,3-bisphosphate intermediate.
9. Enolase catalyzes:
2-phosphoglycerate phosphoenolpyruvate + H2O
C
C
C H 2 O H
O O
H O P O 32
C
C
C H 2 O H
O O
O P O 32
C
C
C H 2
O O
O P O 32
O H
2
3
1
2
3
1
H
2 -p h o s p h o g ly c e r a t e e n o la t e in t e r m e d ia te p h o s p h o e n o lp y r u v a te
E n o la s e
10. Pyruvate Kinase catalyzes: phosphoenolpyruvate + ADP pyruvate + ATP
C
C
CH 3
O O
O2
3
1A D P A T PC
C
CH 2
O O
O PO 32
2
3
1
p h o s p h o e n o l p y r u v a t e p y r u v a t e
P y r u v a t e K i n a s e
C
C
CH 3
O O
O2
3
1A D P A T PC
C
CH 2
O O
O PO 32
2
3
1 C
C
CH 2
O O
O H2
3
1
p h o s p h o e n o l p y r u v a t e e n o l p y r u v a t e p y r u v a t e
P y r u v a t e K i n a s e
Rate Limiting Enzyme
Controlled EnzymeHexokinase
Phosphofructokinase
glucose Glycolysis
ATP
ADP glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
ATP
ADP fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate Isomerase Glycolysis continued
Controlled EnzymeRate
Limiting Enzyme
Glyceraldehyde-3-phosphate Dehydrogenase
Phosphoglycerate Kinase
Enolase
Pyruvate Kinase
glyceraldehyde-3-phosphate
NAD+ + Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate H2O
phosphoenolpyruvate
ADP
ATP pyruvate
controlled Enzyme
ATP Formation
Hexokinase
Phosphofructokinase
glucose Glycolysis
ATP
ADP glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
ATP
ADP fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate Isomerase Glycolysis continued
-1
-1
Glyceraldehyde-3-phosphate Dehydrogenase
Phosphoglycerate Kinase
Enolase
Pyruvate Kinase
glyceraldehyde-3-phosphate
NAD+ + Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate H2O
phosphoenolpyruvate
ADP
ATP pyruvate
Glyceraldehyde-3-phosphate Dehydrogenase
Phosphoglycerate Kinase
Enolase
Pyruvate Kinase
glyceraldehyde-3-phosphate
NAD+ + Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate H2O
phosphoenolpyruvate
ADP
ATP pyruvate
1 NAD 3 ATP
+1 ATP
+1 ATP
Glucose + 2 ADP + 2 NAD+ + 2 Pi -----
> 2 Pyruvate + 2 ATP + 2 NADH + 2 H+
ATP utilized: 2ATP produced: 4NADH produced:2X3= 6
Total : 10- 2 = 8
Energy (Aerobic)
Fates of PyruvateGlucose
2 Pyruvate
2 Ethanol 2 Acetyl-CoA 2 Lactate
4 CO2 + 4 H2O
Glycolysis
2 CO2 –O2 –O2
+O2
+O2 CO2
(yeast) (muscle)
What are the possible fates of pyruvate?
•Ethanol (fermentation)
•Acetyl coA (mammals and others)
• TCA/Krebs cycle
•Lactate (mammals and others)
• End product of anaerobic glycolysis
• Gluconeogenesis in liver via the Cori cycle
The Fate of Pyruvate
In the presence of oxygen pyruvate is transported into the mitochondria where it enters the next major metabolic pathway for the production of ATP energy.
If there is no oxygen present then the pyruvate is converted to a substance called lactate
Gibbs Free Energy Changes
Rxn# Enzyme
1 Hexokinase
2 Phosphogluco-isomerase
3 Phosphofructokinase
4 Aldolase
5 Triose phos. Isomerase
6 G-3-PDH
7 Phosphoglycerate kinase
8 Phosphoglycerate mutas
9 Enolase
10 Pyruvate kinase
11
2
3
10
9
8
7
6
5
4
References :
• Kaplan , Harpers Review,
• Internet
