ATP- The universal energy currency of cell

ATP- structure, synthesis, hydrolysis and functions

1. ATP - the energy currency of cell
Namrata Chhabra, M.D., Biochemistry
Biochemistry for Medics- Lecture notes
www.namrata.co

2. ATP
The nucleotide coenzyme adenosine
triphosphate (ATP) is the most important
form of chemical energy in all cells.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

3. ATP- Structure
ATP is a nucleoside triphosphate containing
adenine, ribose, and three phosphate groups.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

4. Phosphate residues in ATP Structure
•In ATP, a chain of three phosphate residues are
linked to the 5'-OH group of the nucleoside
adenosine .
•These phosphate residues are termed α, β, and γ.
•The α phosphate is bound to ribose by a
phosphoric acid ester bond.
•The linkages between the three phosphate
residues, on the other hand, involve much more
unstable phosphoric acid anhydride bonds.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

5. Phosphate residues in ATP
Structure
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

6. Role of Mg
++
•The active coenzyme is a complex of ATP with
an Mg
2+
ion, which is co-ordinatively bound to
the β and γ phosphates (Mg
2+
ATP
4–
).
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

7. Mechanisms of ATP formation

There are two basic mechanism involved for
ATP formation-
Substrate level phosphorylation and
Oxidative phosphorylation
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

8. 1) Substrate level phosphorylation
•involves phosphorylation of ADP to form ATP
at the expense of the energy of the parent
substrate molecule without involving the
electron transport chain.
•Substrate is a high energy compound as
compared to the product, the surplus energy
is used for ATP formation.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

9. Substrate level phosphorylation in
Glycolysis
•Conversion of 1,3 BPG to 3, Phosphoglycerate
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

10. Substrate level phosphorylation in
Glycolysis
•Conversion of phospho- enol -pyruvate to
Pyruvate
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

11. Substrate level phosphorylation in
TCA Cycle
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

12. Substrate level phosphorylation in
skeletal muscle
 Creatine phosphate, “energy-rich” phosphate compound is formed
from ATP in muscle
 It can regenerate ATP as needed.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

13. 2) ATP by Oxidative phosphorylation
•This process takes place in mitochondria and is energetically coupled to a
proton gradient over a membrane.
•The H
+
gradients established by electron transport chain are used by the
enzyme ATP synthase as a source of energy for direct linking of an
inorganic phosphate to ADP
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

14. Overview of ATP synthesis
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

15. Energy of hydrolysis
•Energy is usually liberated from the ATP
molecule to do work in the cell by a reaction
that removes one of the phosphate-oxygen
groups, leaving adenosine diphosphate (ADP).
•When the ATP converts to ADP, the ATP is said
to be spent.
•Then the ADP is usually immediately recycled
in the mitochondria where it is recharged and
comes out again as ATP.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

16. ATP Hydrolysis
Adenosine attached to
two or one phosphate
residues is called
Adenosine di and mono
phosphate respectively.
The symbol ~ indicates
that the group attached to
the bond, on transfer to an
appropriate acceptor,
results in transfer of the
larger quantity of free
energy.
 For this reason, the term
group transfer potential
rather than "high-energy
bond" is preferred .
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

17. Status of AMP
•The phosphate in AMP (adenosine mono
phosphate) is of the low-energy type, since it
is a normal ester linkage.
•High AMP level depicts a low energy state of
a cell.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

18. Functions of ATP
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

19. Examples of coupling reactions
ATP can donate
single phosphate,
two phosphates or
even Adenosine moiety to suitable acceptors
for the formation of important biological
compounds.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

20. A) Single phosphate transfer
The phosphorylation of glucose to glucose 6-phosphate, the first reaction of
Glycolysis, is highly endergonic and cannot proceed under physiologic conditions.
When (1) and (2) are coupled in a reaction catalyzed by hexokinase,
phosphorylation of glucose readily proceeds in a highly exergonic reaction that
under physiologic conditions is irreversible.

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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

21. B) Transfer of two phosphate groups
During the process of
activation of fatty acid
before oxidation, ATP is
converted to AMP with
the release of
pyrophosphate, which
can subsequently be
hydrolyzed to inorganic
phosphates.
i) Activation of fatty acids
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

22. B) Transfer of two phosphate groups
(contd.)
ii) Activation of amino acids-Amino acids are
activated before incorporation into the
growing peptide chain .
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

23. C) Transfer of adenosine moiety
•This takes place during activation of Methionine to S-
Adenosyl Methionine (Active Methionine), which is a methyl
group donor in the body.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

24. Fate of AMP
•AMP, formed as a consequence of several
activating reactions involving ATP, is
recovered by rephosphorylation to ADP.
•Adenylyl Kinase (Myokinase) interconverts
Adenine Nucleotides
•This enzyme is present in most cells. It
catalyzes the following reaction:
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

25. Reaction catalyzed by Adenylyl kinase
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

26. Why is ATP considered the universal energy
currency of cells why not other nucleotides
like CTP, UTP etc ?
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

27. •The other nucleotides -GTP, CTP and UTP , do
participate in metabolic reactions but the ease
with which ATP can donate single phosphate,
two phosphates, or even Adenosine moiety is
considered a better nucleotide in energy
transfer reactions .
ATP- The energy currency
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

28. Significance of other nucleotides
•GTP has a role in gluconeogenesis and in the
process of translation ; CTP is required for
phospholipid and triacylglycerol synthesis ,
while UTP is required for glycogen synthesis
and also in Uronic pathway for the synthesis
of glycosaminoglycans and for detoxification
reactions.
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

29. References
1) Murray RK, Granner DK, Mayes PA, et al. Harper’s Illustrated
Biochemistry, 28th ed. New York: Lange Medical
Books/McGraw-Hill, 2003.
2) Stryer L: Biochemistry, 6th edition, New York: W.H. Freeman
and company (2002).
3) Lehninger Principles of Biochemistry, Third edition, Macmillan
Worth Publishers, USA(2004).
6) Tietz Text Book of Clinical Chemistry, Third edition, W.B.
Saunders Company, Philadelphia USA (1999).
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry

30. Further reading
Biochemistry for medics- Lecture notes
ATP –the universal energy currency of cell
http://www.namrata.co/atp-the-universal-energy-currency-of-cell/
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Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry