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ATP- The universal energy currency of cell

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ATP- structure, synthesis, hydrolysis and functions

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ATP- The universal energy currency of cell

  1. 1. ATP - the energy currency of cell Namrata Chhabra, M.D., Biochemistry Biochemistry for Medics- Lecture notes www.namrata.co
  2. 2. ATP The nucleotide coenzyme adenosine triphosphate (ATP) is the most important form of chemical energy in all cells. 01/23/16 2 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  3. 3. ATP- Structure ATP is a nucleoside triphosphate containing adenine, ribose, and three phosphate groups. 01/23/16 3 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  4. 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. 01/23/16 4 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  5. 5. Phosphate residues in ATP Structure 01/23/16 5 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  6. 6. 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– ). 01/23/16 6 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  7. 7. Mechanisms of ATP formation There are two basic mechanism involved for ATP formation- Substrate level phosphorylation and Oxidative phosphorylation 01/23/16 7 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  8. 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. 01/23/16 8 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  9. 9. Substrate level phosphorylation in Glycolysis • Conversion of 1,3 BPG to 3, Phosphoglycerate 01/23/16 9 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  10. 10. Substrate level phosphorylation in Glycolysis • Conversion of phospho- enol -pyruvate to Pyruvate 01/23/16 10 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  11. 11. Substrate level phosphorylation in TCA Cycle 01/23/16 11 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  12. 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. 01/23/16 12 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  13. 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 ADP01/23/16 13 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  14. 14. Overview of ATP synthesis 01/23/16 14 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  15. 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. 01/23/16 15 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  16. 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 . 01/23/16 16 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  17. 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. 01/23/16 17 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  18. 18. Functions of ATP 01/23/16 18 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  19. 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. 01/23/16 19 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  20. 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. 01/23/16 20 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  21. 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 01/23/16 21 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  22. 22. B) Transfer of two phosphate groups (contd.) ii) Activation of amino acids-Amino acids are activated before incorporation into the growing peptide chain . 01/23/16 22 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  23. 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. 01/23/16 23 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  24. 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: 01/23/16 24 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  25. 25. Reaction catalyzed by Adenylyl kinase 01/23/16 25 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  26. 26. Why is ATP considered the universal energy currency of cells why not other nucleotides like CTP, UTP etc ? 01/23/16 26 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  27. 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 01/23/16 27 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  28. 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. 01/23/16 28 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  29. 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). 01/23/16 29 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry
  30. 30. Further reading Biochemistry for medics- Lecture notes ATP –the universal energy currency of cell http://www.namrata.co/atp-the-universal-energy-cu 01/23/16 30 Professor (Dr.) Namrata Chhabra, M.D., Biochemistry

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