ATP- The universal energy currency of cell

ATP - the energy currency of cell

Namrata Chhabra, M.D., BiochemistryBiochemistry for Medics- Lecture notes

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ATPThe nucleotide coenzyme adenosine triphosphate (ATP) is the most important form of chemical energy in all cells.

05/03/23 2Professor (Dr.) Namrata Chhabra, M.D., Biochemistry

ATP- Structure

ATP is a nucleoside triphosphate containing adenine, ribose, and three phosphate groups.


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.


Phosphate residues in ATP Structure


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–).


Mechanisms of ATP formation

There are two basic mechanism involved for ATP formation-

Substrate level phosphorylation andOxidative phosphorylation


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.


Substrate level phosphorylation in Glycolysis

• Conversion of 1,3 BPG to 3, Phosphoglycerate


Substrate level phosphorylation in Glycolysis

• Conversion of phospho- enol -pyruvate to Pyruvate


Substrate level phosphorylation in TCA Cycle


Substrate level phosphorylation in skeletal muscle

Creatine phosphate, “energy-rich” phosphate compound is formed from ATP in muscle It can regenerate ATP as needed.


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 ADP05/03/23 13Professor (Dr.) Namrata Chhabra, M.D.,

Biochemistry

Overview of ATP synthesis


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.


ATP HydrolysisAdenosine 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 .


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.


Functions of ATP


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.


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.

05/03/23 20Professor (Dr.) Namrata Chhabra, M.D.,

Biochemistry

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


B) Transfer of two phosphate groups (contd.)

ii) Activation of amino acids-Amino acids are activated before incorporation into the growing peptide chain .


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.


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:


Reaction catalyzed by Adenylyl kinase


Why is ATP considered the universal energy currency of cells why not other nucleotides like CTP, UTP etc ?


• 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


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.


References1) 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).


Further reading

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ATP- The universal energy currency of cell