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.
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.
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
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Ps
o
r
(Dr.) Namrata Chhabra, M.D.,
13
Biochemistry
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.
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:
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