ATP - the energy currency of cell

Namrata Chhabra, M.D., Biochemistry

Biochemistry for Medics- Lecture notes
www.namrata.co
 ATP
The nucleotide coenzyme adenosine
triphosphate (ATP) is the most important
form of chemical energy in all cells.

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

01/23/16 2
Biochemistry
 ATP- Structure

ATP is a nucleoside triphosphate containing

adenine, ribose, and three phosphate groups.
Professor (Dr.) Namrata Chhabra, M.D.,
01/23/16 3
Biochemistry
 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.
Professor (Dr.) Namrata Chhabra, M.D.,
01/23/16 4
Biochemistry
 Phosphate residues in ATP
Structure

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

01/23/16 5
Biochemistry
 Role of Mg++
• The active coenzyme is a complex of ATP with
an Mg2+ion, which is co-ordinatively bound to
the β and γ phosphates (Mg2+ ATP4–).

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

01/23/16 6
Biochemistry
 Mechanisms of ATP formation

There are two basic mechanism involved for

ATP formation-
 Substrate level phosphorylation and

 Oxidative phosphorylation

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

01/23/16 7
Biochemistry
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.

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

01/23/16 8
Biochemistry
 Substrate level phosphorylation in
Glycolysis
• Conversion of 1,3 BPG to 3, Phosphoglycerate

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

01/23/16 9
Biochemistry
 Substrate level phosphorylation in
Glycolysis
• Conversion of phospho- enol -pyruvate to
Pyruvate

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

01/23/16 10
Biochemistry
 Substrate level phosphorylation in
TCA Cycle

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

01/23/16 11
Biochemistry
 Substrate level phosphorylation in
skeletal muscle

 Creatine phosphate, “energy-rich” phosphate compound is formed

from ATP in muscle
 It can regenerate ATP as needed.
Professor (Dr.) Namrata Chhabra, M.D.,
01/23/16 12
Biochemistry
 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
i n organic phosphate toPrAofDesPsor(Dr.) Namrata Chhabra, M.D.,
01/23 / 16
13
Biochemistry
 Overview of ATP synthesis

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

01/23/16 14
Biochemistry
 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.

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

01/23/16 15
Biochemistry
 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
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry "high-energy bond" is
01/23/16 16
Why is ATP hydrolysis an exergonic reaction?
The entropy, which is the level of disorder, of ADP is
greater than that of ATP. Therefore, due to
thermodynamics, the reaction spontaneously occurs
because it wants to be at a higher entropy level. Also,
the Gibbs' free energy of ATP is higher than that of
ADP. Naturally, molecules want to be at a lower
energy state, so equilibrium is shifted towards ADP.
Electrostatic repulsion of the four negative charges on
the oxygens of the ATP molecule. Naturally, like
charges repel and opposite charges attract. Therefore,
Resonance stabilization of ADP and of Pi is greater
than that of ATP. The oxygen molecules of the ADP are
sharing electrons. Those electrons are constantly being
passed back and forth between the oxygens, creating
an effect called resonance. This stabilizes the ADP.
Resonance does not occur in ATP; therefore, it is a
more unstable molecule.
There is a greater degree of solvation of Pi, H+, and
ADP, relative to ATP. This means that it is easier for
ATP to lose one of its phosphate groups. But, it takes a
large amount of water to force ADP to lose one of its
 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.

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

01/23/16 19
Biochemistry
 Functions of ATP

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

01/23/16 20
Biochemistry
 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.

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

01/23/16 21
Biochemistry
 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.
Professor (Dr.) Namrata Chhabra, M.D.,
01/23/16 22
Biochemistry
 B) Transfer of two phosphate groups
i) Activation of fatty acids
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.

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

01/23/16 23
Biochemistry
 B) Transfer of two phosphate groups
(contd.)
ii) Activation of amino acids-Amino acids are
activated before incorporation into the
growing peptide chain .

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

01/23/16 24
Biochemistry
 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.

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

01/23/16 25
Biochemistry
 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:

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

01/23/16 26
Biochemistry
Reaction catalyzed by Adenylyl kinase

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

01/23/16 27
Biochemistry
 Why is ATP considered the universal energy
currency of cells why not other nucleotides
like CTP, UTP etc ?

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

01/23/16 28
Biochemistry
 ATP- The energy currency

• 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 .

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

01/23/16 29
Biochemistry
 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.

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

01/23/16 30
Biochemistry
 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).

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

01/23/16 31
Biochemistry
 Further reading
Biochemistry for medics- Lecture notes
ATP –the universal energy currency of
cell
http://www.namrata.co/atp-the-universal-
energy-c

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

01/23/16 32
Biochemistry