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ATP- the energycurrencyofcell
ATP
Thenucleotide coenzyme adenosine
triphosphate(ATP)is the most important
form of chemicalenergyin all cells.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 2
ATP-Structure
A
TPis anucleoside triphosphate containing
adenine, ribose, and three phosphategroups.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 3
Phosphateresiduesin ATPStructure
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 4
• In ATP
,achain of three phosphate residuesare
linked to the 5'-OH group of the nucleoside
adenosine .
• Thesephosphate residues are termed α, β, andγ.
• Theα phosphate is bound to ribose bya
phosphoric acid esterbond.
• Thelinkages between the three phosphate
residues, on the other hand, involve muchmore
unstable phosphoric acid anhydridebonds.
Phosphateresiduesin ATP
Structure
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 5
Roleof Mg++
• The active coenzyme is a complex of ATPwith
an Mg2+ion, which is co-ordinatively bound to
the β and γ phosphates (Mg2+ATP4–).
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 6
Mechanismsof ATPformation
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 7
There are two basic mechanism involvedfor
ATPformation-
Substrate level phosphorylationand
Oxidative phosphorylation
1) Substratelevel phosphorylation
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 8
• involves phosphorylation of ADPto formATP
at the expenseof the energy of the parent
substrate molecule without involving the
electron transport chain.
• Substrate is ahigh energy compound as
compared to the product, the surplus energy
is used for ATPformation.
Substrate level phosphorylationin
Glycolysis
• Conversion of 1,3 BPGto 3,Phosphoglycerate
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 9
Substrate level phosphorylationin
Glycolysis
• Conversion of phospho- enol -pyruvateto
Pyruvate
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 10
Substrate level phosphorylationin
TCACycle
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 11
Substrate level phosphorylationin
skeletal muscle
 Creatine phosphate, “energy-rich” phosphate compound is formed
from ATPinmuscle
 It can regenerateATPasneeded.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 12
2) ATPbyOxidativephosphorylation
•
•
Thisprocesstakes place in mitochondria and is energetically coupled to a
proton gradient over amembrane.
TheH+gradients established by electron transport chain are usedby the
enzyme ATPsynthaseasasource of energy for direct linking ofan
01/23i/n16organicphosphate toP
r
Ao
f
De
s
Ps
o
r
(Dr.) Namrata Chhabra, M.D.,
13
Biochemistry
Overview of ATPsynthesis
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 14
Energyof hydrolysis
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 15
• Energy is usually liberated from the ATP
molecule to do work in the cell by areaction
that removes one of the phosphate-oxygen
groups, leaving adenosine diphosphate (ADP).
• When the ATPconverts to ADP
,the ATPis said
to bespent.
• Then the ADPis usually immediately recycled
in the mitochondria where it is recharged and
comes out again asATP
.
ATPHydrolysis
Adenosine attachedto
two or one phosphate
residues is called
Adenosinedi andmono
phosphaterespectively.
The symbol ~indicates
that the group attached to
the bond, on transfer toan
appropriate acceptor,
results in transfer ofthe
larger quantity of free
energy.
 For this reason, the term
grouptransferpotential
rather than "high-energy
bond" is preferred.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 16
Statusof AMP
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 17
• Thephosphate in AMP(adenosine mono
phosphate) is of the low-energy type,since it
is anormal ester linkage.
• HighAMPlevel depicts alow energy stateof
acell.
Functionsof ATP
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 18
Examplesof coupling reactions
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 19
ATPcandonate
single phosphate,
two phosphatesor
evenAdenosine moiety to suitable acceptors
for the formation of important biological
compounds.
A)Singlephosphate transfer
The phosphorylation of glucose to glucose 6-phosphate, the first reaction of
Glycolysis, is highly endergonic and cannot proceed under physiologicconditions.
When (1) and (2) are coupled in areaction catalyzed by hexokinase,
phosphorylation of glucose readily proceeds in ahighly exergonic reactionthat
under physiologic conditions isirreversible.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 20
B)Transferof two phosphate groups
During the process of
activation of fatty acid
before oxidation, ATPis
converted to AMPwith
the release of
pyrophosphate, which
cansubsequently be
hydrolyzed to inorganic
phosphates.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 21
i) Activation of fattyacids
B)Transferof two phosphategroups
(contd.)
ii) Activation of amino acids-Aminoacids are
activated before incorporation into the
growing peptide chain.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 22
C)Transferof adenosinemoiety
• Thistakes place during activation of Methionine to S-
Adenosyl Methionine (Active Methionine), which is amethyl
group donor in thebody.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 23
Fate of AMP
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 24
• AMP, formed asaconsequence of several
activating reactions involving ATP
,is
recovered by rephosphorylation toADP
.
• Adenylyl Kinase(Myokinase) interconverts
Adenine Nucleotides
• This enzymeis present in most cells.It
catalyzes the following reaction:
Reactioncatalyzed byAdenylyl kinase
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 25
Why isATP consideredthe universalenergy
currencyof cellswhynot other nucleotides
like CTP,UTPetc?
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 26
• Theother nucleotides -GTP
,CTPand UTP, do
participate in metabolic reactions but the ease
with which ATPcan donate single phosphate,
two phosphates, or evenAdenosine moiety is
considered abetter nucleotide in energy
transfer reactions.
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 27
ATP-Theenergy currency
Significanceof other nucleotides
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 28
• GTPhasarole in gluconeogenesis and in the
process of translation ; CTPis required for
phospholipid and triacylglycerol synthesis ,
while UTPis required for glycogen synthesis
and also in Uronic pathway for thesynthesis
of glycosaminoglycans and for detoxification
reactions.
References
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 29
1) Murray RK,Granner DK,Mayes PA,et al. Harper’s Illustrated
Biochemistry, 28th ed. New York: LangeMedical
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.
SaundersCompany, Philadelphia USA(1999).
Further reading
Professor (Dr.) Namrata Chhabra, M.D.,
Biochemistry
01/23/16 30
Biochemistry for medics- Lecture notes
ATP –the universalenergy currency of cell
http://www.namrata.co/atp-the-universal-energy-c

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ATP- the energy currency of cell

  • 2. ATP Thenucleotide coenzyme adenosine triphosphate(ATP)is the most important form of chemicalenergyin all cells. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 2
  • 3. ATP-Structure A TPis anucleoside triphosphate containing adenine, ribose, and three phosphategroups. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 3
  • 4. Phosphateresiduesin ATPStructure Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 4 • In ATP ,achain of three phosphate residuesare linked to the 5'-OH group of the nucleoside adenosine . • Thesephosphate residues are termed α, β, andγ. • Theα phosphate is bound to ribose bya phosphoric acid esterbond. • Thelinkages between the three phosphate residues, on the other hand, involve muchmore unstable phosphoric acid anhydridebonds.
  • 5. Phosphateresiduesin ATP Structure Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 5
  • 6. Roleof Mg++ • The active coenzyme is a complex of ATPwith an Mg2+ion, which is co-ordinatively bound to the β and γ phosphates (Mg2+ATP4–). Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 6
  • 7. Mechanismsof ATPformation Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 7 There are two basic mechanism involvedfor ATPformation- Substrate level phosphorylationand Oxidative phosphorylation
  • 8. 1) Substratelevel phosphorylation Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 8 • involves phosphorylation of ADPto formATP at the expenseof the energy of the parent substrate molecule without involving the electron transport chain. • Substrate is ahigh energy compound as compared to the product, the surplus energy is used for ATPformation.
  • 9. Substrate level phosphorylationin Glycolysis • Conversion of 1,3 BPGto 3,Phosphoglycerate Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 9
  • 10. Substrate level phosphorylationin Glycolysis • Conversion of phospho- enol -pyruvateto Pyruvate Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 10
  • 11. Substrate level phosphorylationin TCACycle Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 11
  • 12. Substrate level phosphorylationin skeletal muscle  Creatine phosphate, “energy-rich” phosphate compound is formed from ATPinmuscle  It can regenerateATPasneeded. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 12
  • 13. 2) ATPbyOxidativephosphorylation • • Thisprocesstakes place in mitochondria and is energetically coupled to a proton gradient over amembrane. TheH+gradients established by electron transport chain are usedby the enzyme ATPsynthaseasasource of energy for direct linking ofan 01/23i/n16organicphosphate toP r Ao f De s Ps o r (Dr.) Namrata Chhabra, M.D., 13 Biochemistry
  • 14. Overview of ATPsynthesis Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 14
  • 15. Energyof hydrolysis Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 15 • Energy is usually liberated from the ATP molecule to do work in the cell by areaction that removes one of the phosphate-oxygen groups, leaving adenosine diphosphate (ADP). • When the ATPconverts to ADP ,the ATPis said to bespent. • Then the ADPis usually immediately recycled in the mitochondria where it is recharged and comes out again asATP .
  • 16. ATPHydrolysis Adenosine attachedto two or one phosphate residues is called Adenosinedi andmono phosphaterespectively. The symbol ~indicates that the group attached to the bond, on transfer toan appropriate acceptor, results in transfer ofthe larger quantity of free energy.  For this reason, the term grouptransferpotential rather than "high-energy bond" is preferred. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 16
  • 17. Statusof AMP Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 17 • Thephosphate in AMP(adenosine mono phosphate) is of the low-energy type,since it is anormal ester linkage. • HighAMPlevel depicts alow energy stateof acell.
  • 18. Functionsof ATP Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 18
  • 19. Examplesof coupling reactions Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 19 ATPcandonate single phosphate, two phosphatesor evenAdenosine moiety to suitable acceptors for the formation of important biological compounds.
  • 20. A)Singlephosphate transfer The phosphorylation of glucose to glucose 6-phosphate, the first reaction of Glycolysis, is highly endergonic and cannot proceed under physiologicconditions. When (1) and (2) are coupled in areaction catalyzed by hexokinase, phosphorylation of glucose readily proceeds in ahighly exergonic reactionthat under physiologic conditions isirreversible. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 20
  • 21. B)Transferof two phosphate groups During the process of activation of fatty acid before oxidation, ATPis converted to AMPwith the release of pyrophosphate, which cansubsequently be hydrolyzed to inorganic phosphates. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 21 i) Activation of fattyacids
  • 22. B)Transferof two phosphategroups (contd.) ii) Activation of amino acids-Aminoacids are activated before incorporation into the growing peptide chain. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 22
  • 23. C)Transferof adenosinemoiety • Thistakes place during activation of Methionine to S- Adenosyl Methionine (Active Methionine), which is amethyl group donor in thebody. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 23
  • 24. Fate of AMP Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 24 • AMP, formed asaconsequence of several activating reactions involving ATP ,is recovered by rephosphorylation toADP . • Adenylyl Kinase(Myokinase) interconverts Adenine Nucleotides • This enzymeis present in most cells.It catalyzes the following reaction:
  • 25. Reactioncatalyzed byAdenylyl kinase Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 25
  • 26. Why isATP consideredthe universalenergy currencyof cellswhynot other nucleotides like CTP,UTPetc? Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 26
  • 27. • Theother nucleotides -GTP ,CTPand UTP, do participate in metabolic reactions but the ease with which ATPcan donate single phosphate, two phosphates, or evenAdenosine moiety is considered abetter nucleotide in energy transfer reactions. Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 27 ATP-Theenergy currency
  • 28. Significanceof other nucleotides Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 28 • GTPhasarole in gluconeogenesis and in the process of translation ; CTPis required for phospholipid and triacylglycerol synthesis , while UTPis required for glycogen synthesis and also in Uronic pathway for thesynthesis of glycosaminoglycans and for detoxification reactions.
  • 29. References Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 29 1) Murray RK,Granner DK,Mayes PA,et al. Harper’s Illustrated Biochemistry, 28th ed. New York: LangeMedical 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. SaundersCompany, Philadelphia USA(1999).
  • 30. Further reading Professor (Dr.) Namrata Chhabra, M.D., Biochemistry 01/23/16 30 Biochemistry for medics- Lecture notes ATP –the universalenergy currency of cell http://www.namrata.co/atp-the-universal-energy-c