The Adenosine triphosphate The Adenosine triphosphate (ATP)(ATP)

Lecture no 6

The Adenosine triphosphate (ATP)The Adenosine triphosphate (ATP)

Adenosine-5'-triphosphate (ATP) is a multifunctional nucleotide used in cells as a coenzyme.

ATP transports chemical energy within cells.

ATP is produced by phosphorylation and cellular respiration and used by enzymes and structural proteins in many cellular processes, including:

- Metabolism, synthesis, and active transport.Metabolism, synthesis, and active transport. - Roles in cell structure and locomotion. - Cell signaling.

Lecture no 6

Lecture no 6

One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase from inorganic phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP).

Lecture no 6

Metabolic processes that use ATP as an energy source convert it back into its precursors. ATP is therefore continuously recycled in organisms, with the human body turning over its own weight in ATP each day

Lecture no 6

Structure and properties of ATPStructure and properties of ATPATPATP is a nucleotide consists of adenine (6 is a nucleotide consists of adenine (6

amino derivative of purine, the 5-carbon amino derivative of purine, the 5-carbon sugar,ribose, attached to adenine through sugar,ribose, attached to adenine through

glucosyl linkage and 3 phosphate group joined glucosyl linkage and 3 phosphate group joined to 5‘-position of ribose.to 5‘-position of ribose.

ATP, ADP and AMP occur in all cells.ATP, ADP and AMP occur in all cells.

Lecture no 6

The phosphoryl groups, starting with the group closest to the ribose, are referred to as the (α), (β), and (γ) phosphates.

ATP molecule as it exists in the intact cell is highly ATP molecule as it exists in the intact cell is highly charged at pH 7, the three phosphate groups are charged at pH 7, the three phosphate groups are completely ionized (4 negative charges) near the completely ionized (4 negative charges) near the linear phosphate structure.linear phosphate structure.

Lecture no 6

ATP is high energy compound because it has a ATP is high energy compound because it has a large negative free energy of hydrolysis.large negative free energy of hydrolysis.

Two phosphoanhydride bonds (those that connect adjacent phosphates) in an ATP molecule are

responsible for the high energy content of this molecule.

The first phosphate of The first phosphate of

ATP is an ester bonded ATP is an ester bonded

phosphate and this is notphosphate and this is not

a high energy bond.a high energy bond.

Lecture no 6

These anhydride bonds are frequently referred to as high-energy bonds.

Energy stored in ATP maybe released upon hydrolysis of the anhydride bonds.

Lecture no 6

ATP Hydrolysis

When ATP is incubated under suitable When ATP is incubated under suitable conditions with muscle fibers, it undergoes conditions with muscle fibers, it undergoes enzymatic hydrolysis to give ADP +Pi enzymatic hydrolysis to give ADP +Pi

When this hydrolysis proceeds it gives large When this hydrolysis proceeds it gives large liberation of heat.liberation of heat.

Lecture no 6

The bonds formed after hydrolysis—or the phosphorylation of a residue by ATP—are lower in energy than the phosphoanhydride bonds of ATP.

During enzyme-catalyzed hydrolysis of ATP or phosphorylation by ATP, the available free energy can be harnessed by a living system to do work.

Compounds with Compounds with ΔΔ G more negative than 7 G more negative than 7 Kcal/mole or 30 KJ/ mole are regarded as high Kcal/mole or 30 KJ/ mole are regarded as high energy compounds.energy compounds.

Lecture no 6

The overall equation for ATP hydrolysis is usually written:

ATP + H2O <=> ADP + inorganic phosphate (Pi)

ΔGo' = -7.3 kcal. mol-1Note, the H2O is omitted from the logarithmic term because it is the solvent with a standard state of 1M.

Lecture no 6

Mechanism of ATP hydrolysisMechanism of ATP hydrolysis

When the terminal phosphate bond is When the terminal phosphate bond is hydrolyzed, some electrostatic stress is hydrolyzed, some electrostatic stress is

relieved, the similar charges are separated as relieved, the similar charges are separated as ADPADP3-3- + HPO + HPO44 2-2- and they will have very little and they will have very little

tendency to combine again because their tendency to combine again because their similar charges repel each other.similar charges repel each other.

ATP ATP 4-4- + H + H22OO ADPADP3-3- + HPO + HPO44 2-2-

ADP and phosphate as soon as they are ADP and phosphate as soon as they are formed undergo stabilization by resonance.formed undergo stabilization by resonance.

Lecture no 6

Ionization in biological systems

ATP has several negatively-charged groups in neutral solution, it can chelate metals with very high affinity.

ATP forms stable complexes with certain ATP forms stable complexes with certain divalent cations as Mgdivalent cations as Mg2+. 2+. Most of ATP in the cell Most of ATP in the cell present as Mgpresent as Mg2+2+-complex Mg-complex Mg2+.2+.

Lecture no 6

Why G°' is so high for ATP hydrolysisWhy G°' is so high for ATP hydrolysis??

Hydrolysis reduces electrostatic repulsion between Hydrolysis reduces electrostatic repulsion between negative charged oxygen atoms on the phosphorus negative charged oxygen atoms on the phosphorus atomsatoms..

ADP and Pi are stabilised by resonanceADP and Pi are stabilised by resonance..

Entropy (disorder) is higher after the reaction.Entropy (disorder) is higher after the reaction.

These 3 factors make ATP hydrolysis favourable These 3 factors make ATP hydrolysis favourable and are responsible for the large amount of energy and are responsible for the large amount of energy released during hydrolysis. released during hydrolysis.

Lecture no 6

However, there are a number of factors which make the true situation more complicated. Most important are:

1- The conc of ATP, ADP and Pi in the cell are The conc of ATP, ADP and Pi in the cell are much lower than 1.0 M much lower than 1.0 M .

2-These substances are not present in equimolar 2-These substances are not present in equimolar concentrationsconcentrations

2- The presence of Mg2+ will also modify the value for Δ Go, because the different reactants form complexes with bivalent cations.

Lecture no 6

If appropriate corrections are applied of all these If appropriate corrections are applied of all these factors, the free energy of hydrolysis of ATP to factors, the free energy of hydrolysis of ATP to

ADP under intracellular conditions will be about -ADP under intracellular conditions will be about -12 Kcal/ mole.12 Kcal/ mole.

So free energy of ATP hydrolysis inside cells is So free energy of ATP hydrolysis inside cells is not necessarily constant.not necessarily constant.

Free energy of ATP vary from one cell to another.Free energy of ATP vary from one cell to another.

It may vary from time to time depending on the It may vary from time to time depending on the concentration of Mgconcentration of Mg2+, 2+, ATP, ADP and Pi.ATP, ADP and Pi.

Lecture no 6

ATP synthesisATP synthesis

For ATP synthesis, the reaction is written in the reverse direction, and the sign of the free energy change is reversed, so that:

ADP + inorganic phosphate (Pi) <=> ATP + H2O

ΔGo' = +7.3 kcal. mol-1

The modifying factors which affect the hydrolysis also effect the reverse reaction

Lecture no 6