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Biosynthesis of Nucleotides & Phosphoguanidines Through Coupled
Reactions
Term paper submitted in partial fulfilment of requirements for the award for the degree of
Master of Science
in
Applied Chemistry
Submitted by
Tanisha Mendiratta
M.Sc Semester II
Enrollment No: A51650918001
Academic Session 2018-2020
April 2019
INTRODUCTION
 Adenosine triphosphate (ATP) is energy currency in our body.
 ATP contains
1. A nitrogenous base – Adenine
2. A sugar – Ribose
3. Three Phosphate Groups
 Whenever a body needs energy beta – gamma phosphate bonds of ATP is hydrolyzed to
create the ADP and a free phosphate molecule.
 ATP forms by the processes – Citric acid cycle and Glycolysis.
Fig. Structure of ATP
Continue…
ATP + H2O AMP + PPi 10Kcal/mol - (1)
ATP + AMP ADP + ADP - (2)
ATP ADP + Pi - (3)
High energy bonds of ATP
 Phosphoanhydride
linkages are said to be
high energy bonds.
 ∆G of hydrolysis is high,
not bond energy.
N
N
NH
N
NH2
H
C
O
C
CH2
C
OH OH
H H
H
CH2OP
O
O
–
OP
O
O
–
OP
O
O
–
O
–
Phosphoanhydride
bonds
Adenosine
AMP
ADP
ATP
Phosphoester
bonds
Factors responsible for the “high-energy”
character of phosphoanhydride bond
1. The resonance stabilization of phosphoanhydride
bond less than that of its hydrolysis products.
2. Greater importance is the destabilizing effect of the
electrostatic repulsion.
3. The high phosphoryl group transfer potential of
Phosphocreatine result from the competing
resonance in guanidino group.
Coupled Reaction
 The exergonic hydrolysis of ATP is coupled with
endergonic dehydration process by transferring a
phosphate group to another molecule.
 Coupled reaction has net exergonic effect so will
occur spontaneously.
ATP + H2O ADP + Pi - (1)
Hydrolysis
∆𝐺° = −30.5𝐾 𝐽 𝑚 𝑜𝑙
Creatine + Pi PCr + H2O - (2) ∆𝐺° = +44.1𝐾 𝐽 𝑚 𝑜𝑙
Chemical reactions are additive.
Sum ATP + Cr ADP + PCr ∆𝐺 = 12.6 𝐾 𝐽 𝑚 𝑜𝑙
Results and Discussion
When Keq is ∆G˚ is Starting with 1M conc.
>1.0 negative Proceeds forward
1.0 0 Remains at equilibrium
<1.0 positive Proceeds backward
Table 1.Relationship among Keq,
∆G and the direction of chemical
reaction.
 The free energy change for ATP
hydrolysis is large and negative.
 The hydrolytic cleavage of terminal
phosphoanhydride bond in ATP
separate one of the 3 negatively
charged phosphate and also some
of the internal electrostatic
repulsion.
Fig. Transference of free energy from an
exergonic to an endergonic reaction
through the formation of high energy
intermediate compound.
Continue
 Range of intracellular ATP – 2.0 – 10.0 mM
 Consider a typical cell with
 ATP – 3.0 mM
 ADP – 0.8 mM
 Pi – 4.0 mM Eq. Used to calculate concentration of
particular chemical species.
∆G = −30.5𝐾𝐽𝑚𝑜𝑙−1
+ (8.314 𝐽𝑘−1
)(310𝐾) 𝑙𝑛(
0.8 × 10−3
𝑀 4.0 × 10−3
𝑀
3.0 × 10−3 𝑀
)
Conclusion
 The free energy change for the reaction of ATP
regeneration is not depends on the path, it mainly
depends on the nature and the concentration of
reactant and the product.
 Now it is seen that synthesis of nucleotide and
phosphoguanidines in voluntary and non-voluntary
muscle is carried by the same mechanism.
E
Endergonic Processes Synthesis
Muscular Contractions
Nervous excitation
Active Transport
1
2
3
4
Exergonic
Reaction
REFERENCES
 Ferreira L.G , 2014 .
 Jain J L, Jain. S, Jain N, ISBN: 81-219-3907-0.
 Min K.L, Steghens J.P, Henry. R, Doutheau. A,
Collombel. C 1997, DOI: 10.1016/S0167-
4838(97)00088-5.
 Powar C.B, Chatwal G.R, ISBN: 978-81-
8318-910-1.
 Voet. D, Voet J.G, Pratt C.W, ISBN: 0-471-
58650-1.
 Nelson D.L, M.CoX .M, and ISBN-13: 978-1-
4641-2611-6, ISBN-10: 1-4641-2611-9.

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Tanisha ppt

  • 1. Biosynthesis of Nucleotides & Phosphoguanidines Through Coupled Reactions Term paper submitted in partial fulfilment of requirements for the award for the degree of Master of Science in Applied Chemistry Submitted by Tanisha Mendiratta M.Sc Semester II Enrollment No: A51650918001 Academic Session 2018-2020 April 2019
  • 2. INTRODUCTION  Adenosine triphosphate (ATP) is energy currency in our body.  ATP contains 1. A nitrogenous base – Adenine 2. A sugar – Ribose 3. Three Phosphate Groups  Whenever a body needs energy beta – gamma phosphate bonds of ATP is hydrolyzed to create the ADP and a free phosphate molecule.  ATP forms by the processes – Citric acid cycle and Glycolysis. Fig. Structure of ATP
  • 3. Continue… ATP + H2O AMP + PPi 10Kcal/mol - (1) ATP + AMP ADP + ADP - (2) ATP ADP + Pi - (3)
  • 4. High energy bonds of ATP  Phosphoanhydride linkages are said to be high energy bonds.  ∆G of hydrolysis is high, not bond energy. N N NH N NH2 H C O C CH2 C OH OH H H H CH2OP O O – OP O O – OP O O – O – Phosphoanhydride bonds Adenosine AMP ADP ATP Phosphoester bonds
  • 5. Factors responsible for the “high-energy” character of phosphoanhydride bond 1. The resonance stabilization of phosphoanhydride bond less than that of its hydrolysis products. 2. Greater importance is the destabilizing effect of the electrostatic repulsion. 3. The high phosphoryl group transfer potential of Phosphocreatine result from the competing resonance in guanidino group.
  • 6. Coupled Reaction  The exergonic hydrolysis of ATP is coupled with endergonic dehydration process by transferring a phosphate group to another molecule.  Coupled reaction has net exergonic effect so will occur spontaneously. ATP + H2O ADP + Pi - (1) Hydrolysis ∆𝐺° = −30.5𝐾 𝐽 𝑚 𝑜𝑙 Creatine + Pi PCr + H2O - (2) ∆𝐺° = +44.1𝐾 𝐽 𝑚 𝑜𝑙 Chemical reactions are additive. Sum ATP + Cr ADP + PCr ∆𝐺 = 12.6 𝐾 𝐽 𝑚 𝑜𝑙
  • 7. Results and Discussion When Keq is ∆G˚ is Starting with 1M conc. >1.0 negative Proceeds forward 1.0 0 Remains at equilibrium <1.0 positive Proceeds backward Table 1.Relationship among Keq, ∆G and the direction of chemical reaction.  The free energy change for ATP hydrolysis is large and negative.  The hydrolytic cleavage of terminal phosphoanhydride bond in ATP separate one of the 3 negatively charged phosphate and also some of the internal electrostatic repulsion. Fig. Transference of free energy from an exergonic to an endergonic reaction through the formation of high energy intermediate compound.
  • 8. Continue  Range of intracellular ATP – 2.0 – 10.0 mM  Consider a typical cell with  ATP – 3.0 mM  ADP – 0.8 mM  Pi – 4.0 mM Eq. Used to calculate concentration of particular chemical species. ∆G = −30.5𝐾𝐽𝑚𝑜𝑙−1 + (8.314 𝐽𝑘−1 )(310𝐾) 𝑙𝑛( 0.8 × 10−3 𝑀 4.0 × 10−3 𝑀 3.0 × 10−3 𝑀 )
  • 9. Conclusion  The free energy change for the reaction of ATP regeneration is not depends on the path, it mainly depends on the nature and the concentration of reactant and the product.  Now it is seen that synthesis of nucleotide and phosphoguanidines in voluntary and non-voluntary muscle is carried by the same mechanism. E Endergonic Processes Synthesis Muscular Contractions Nervous excitation Active Transport 1 2 3 4 Exergonic Reaction
  • 10. REFERENCES  Ferreira L.G , 2014 .  Jain J L, Jain. S, Jain N, ISBN: 81-219-3907-0.  Min K.L, Steghens J.P, Henry. R, Doutheau. A, Collombel. C 1997, DOI: 10.1016/S0167- 4838(97)00088-5.  Powar C.B, Chatwal G.R, ISBN: 978-81- 8318-910-1.  Voet. D, Voet J.G, Pratt C.W, ISBN: 0-471- 58650-1.  Nelson D.L, M.CoX .M, and ISBN-13: 978-1- 4641-2611-6, ISBN-10: 1-4641-2611-9.