The Adenosine triphosphate (ATP)

1. Lecture no 6 The Adenosine triphosphate (ATP)

2. Lecture no 6 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. - Roles in cell structure and locomotion. - Cell signaling.

3. Lecture no 6

4. 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).

5. 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

6. Lecture no 6 Structure and properties of ATP ATP is a nucleotide consists of adenine (6 amino derivative of purine, the 5-carbon sugar,ribose, attached to adenine through glucosyl linkage and 3 phosphate group joined to 5‘-position of ribose. ATP, ADP and AMP occur in all cells.

7. 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 charged at pH 7, the three phosphate groups are completely ionized (4 negative charges) near the linear phosphate structure.

8. ATP is high energy compound because it has a large negative free energy of hydrolysis. Twophosphoanhydridebonds (those that connect adjacent phosphates) in an ATP molecule are responsible for the high energy content of this molecule. The first phosphate of ATP is an ester bonded phosphate and this is not a high energy bond. Lecture no 6

9. Lecture no 6 • These anhydride bonds are frequently referred to ashigh-energy bonds. • Energy stored in ATP maybe released uponhydrolysisof the anhydride bonds.

10. Lecture no 6 ATP Hydrolysis • When ATP is incubated under suitable conditions with muscle fibers, it undergoes enzymatic hydrolysis to give ADP +Pi • When this hydrolysis proceeds it gives large liberation of heat.

11. 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 Δ G more negative than 7 Kcal/mole or 30 KJ/ mole are regarded as high energy compounds.

12. Lecture no 6 • The overall equation for ATP hydrolysis is usually written: ATP + H2O <=> ADP + inorganic phosphate (Pi) • ΔGo' = -7.3 kcal. mol-1 • Note, the H2O is omitted from the logarithmic term because it is the solvent with a standard state of 1M.

13. Lecture no 6 Mechanism of ATP hydrolysis When the terminal phosphate bond is hydrolyzed, some electrostatic stress is relieved, the similar charges are separated as ADP3- + HPO42-and they will have very little tendency to combine again because their similar charges repel each other. ATP 4- + H2OADP3- + HPO42- ADP and phosphate as soon as they are formed undergo stabilization by resonance.

14. Lecture no 6 Ionization in biological systems ATP has several negatively-charged groups in neutral solution, it canchelatemetals with very high affinity. ATP forms stable complexes with certain divalent cations as Mg2+. Most of ATP in the cell present as Mg2+-complex Mg2+.

15. Lecture no 6 Why G°' is so high for ATP hydrolysis? • Hydrolysis reduces electrostatic repulsion between negative charged oxygen atoms on the phosphorus atoms. • ADP and Pi are stabilised by resonance. • Entropy (disorder) is higher after the reaction. These 3 factors make ATP hydrolysis favourable and are responsible for the large amount of energy released during hydrolysis.

16. 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 much lower than 1.0 M . 2-These substances are not present in equimolar concentrations 2- The presence of Mg2+ will also modify the value for Δ Go, because the different reactants form complexes with bivalent cations.

17. Lecture no 6 • If appropriate corrections are applied of all these factors, the free energy of hydrolysis of ATP to ADP under intracellular conditions will be about -12 Kcal/ mole. • So free energy of ATP hydrolysis inside cells is not necessarily constant. • Free energy of ATP vary from one cell to another. • It may vary from time to time depending on the concentration of Mg2+, ATP, ADP and Pi.

18. Lecture no 6 ATP 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