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BIO 202 Biochemistry II
bySeyhun YURDUGL
Lecture 2Metabolism and Thermodynamics
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Content Outline Metabolism
Bioenergetics
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Background Living organisms are not at equilibrium
Metabolism: process by which livingsystems acquire & use energy
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How living things obtain energy Living organisms may be:
Autotrophs (Phototrophs)
self- or light- feeders
Energy from sun
Make carbohydrates Give off O2
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How living things obtain energy Heterotrophs (Chemotrophs)
Provide food by chemical feeders
CO2 returned to atmosphere
Free energyproduced here: used to makeATP
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Metabolism Metabolism consists of two contrasting
phases
Anabolism (Formation of metabolites)
Catabolism (Degradation of metabolites)
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Metabolism regulated at 3 levels
Action of allosteric enzymes
Hormonal regulation
Auto-regulation of enzyme concentrationwithin cells
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General definition of metabolism The sum of chemical changes
that convert foodstuffs into usable forms ofenergy
and into complex biological molecules
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Principles of Bioenergetics Energy use: fundamental to living
organisms
Bioenergetics: quantitative studyofenergy transductions occurring in livingcells
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Catabolism Degradation of ingested foodstuffs
or stored fuels such as
carbohydrate, lipid and protein into eitherusable forms of energy.
generally results in conversion of largecomplex molecules to smaller moleculeslike CO2, and H2O.
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Anabolism Involved in biosynthesis of large, complex
molecules from smaller precursors
require expenditure of energy
either in the form of ATP
or using reducing equivalents stored inNADPH.
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Catabolism By the oxidative reactions of catabolism,
transfer of reducing equivalents to thecoenzymes NAD+ and NADP+:
to form NADH and NADPH, and a proton,H+
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Catabolism In mammals these reactions often require
consumption of molecular oxygen.
perform various necessary and tissue-specific cellular functions:
e.g. nerve impulse conduction, muscle
contraction, growth and cell division.
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ATP Adenosine-5-triphosphate
Purine(adenine) nucleotide in whichadenine:
attached in a glycosidic linkage to D-ribose
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ATP Three phosphoryl groups:
esterified to the 5 position of the ribosemoiety in phosphoanhydride bonds
Two terminal phosphoryl groups(i.e. and) designated as energy-rich;
or high energy bonds.
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Structure of ATP
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Pyridine nucleotides:
The pyridine nucleotide coenzymes
NADH / NAD+
and NADPH / NADP+
are synthesized from nicotinamide (niacin,vitamin B3)
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Pyridine nucleotides:
the principal mobile carriers of reducingequivalents;
between soluble dehydrogenase enzymesand the respiratory chain.
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Flavins:
The flavin derivatives:
FAD and FMN:
synthesized from dietary riboflavin (vitaminB2).
are most commonly encountered asprosthetic groups,
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Flavins:
permanently attached to enzymes involvedin redox reactions,
where they function as temporary carriers ofreducing equivalents;
as part of the catalytic mechanism
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Quantities that describe energy
changes in chemical reactions:
G: Gibbs Free Energy
G = free energy change
- G = exergonic reaction
+ G = endergonic reaction
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Quantities that describe energy
changes in chemical reactions: H: Enthalpy (heat content)
-H: exothermic
+H: endothermic
S: Entropy+S = entropy increase
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Quantities that describe energy
changes in chemical reactions:
At constant temperature & pressure:
G = H - TS
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Quantities that describe energy
changes in chemical reactions:
In any favorable process,
S is +
H is - G is -
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Cells require sources offree
energy
Heat denatures proteins
Must be acquired from sun or food
Free energy converted to ATP
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Free energy and cells Standard free energy change (Gr) is related to
Keq
Mix of reactants, products change untilequilibrium is reached Concentrations and equilibrium define Keq
Standard TransformedConstants: Gr, Keq
25oC pH=7 Water = 55.5M
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For biochemical reactions:
G=0, at equilibrium
Standard Transformed Constants:
25oC (298oK)
pH=7
Water = 55.5M
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Tendency toward equilibrium is a
driving force
Expressed as G0
Relationship between Keq & G0:
G0 = -RT ln Keq
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Standard free energy change is an alternativeway to express equilibrium constant
If Keq = 1.0, G0 = 0
If Keq = >1.0, G0 is negative
If Keq =
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Actual free energy change depends on
concentrations of reactants & products
Must distinguish between
actual energy change (G) and
standard free energy change (G0)
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Free energy and equilibrium G: changes as reaction approaches
equilibrium
Determines spontaneity of reaction
G0: tells in which direction reaction willgo to reach equilibrium
G0 is a constant
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Free energy and equilibrium G and G0:
theoretical maximum energy a reaction candeliver
Free energy change (G0) is independentof the reaction pathway
Depends only on the nature andconcentration of reactants and products
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Standard free energy changes are
additive
Each reaction in a sequence has its own Keq& Gr
Gr of sequential reactions are additive
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Standard free energy changes are
additive
Biologically, explains how reactions may bedriven by coupling:
Example: synthesis of Glucose-6-P
Glucose + Pi Glucose-6-P + H20
ATP + H20 ADP + Pi
ATP + Glucose ADP + Glucose-6-P
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Standard free energy changes are
additive
Overall, reaction is exergonic But when energy from ATP used to drive
Glu-6-P synthesis is in consideration:
This reaction is endergonic
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Phosphoryl Group Transfers & ATP
ATP: most common form of cellularenergy
Heterotrophs obtain free energy fromnutrients
Free energy used to make ATP
Involves transfer of phosphoryl groups
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G for ATP hydrolysis is large &negative. Why?
Several factors:
Resonance stabilization ofphosphoanhydride bond :
most favorable in a hydrolyzed bond
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G for ATP hydrolysis is large &negative. Why?
Negative charge repulsions on ATP:relieved by hydrolysis
Smaller solvation energy of aphosphoanhydride
compared to its hydrolysis product
may provide dominant force forATP hydrolysis
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G for ATP hydrolysis is large &negative. Why?
Cleavage of a phosphate relieveselectrostatic repulsion
ADP ionizes, releasing H+
The low [H+], the direct product, favorshydrolysis
Occurs only in presence of an enzyme
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ATP Hydrolysis
Chemical basis for the large G0 associatedwith ATP hydrolysis
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Other phosphorylated compounds & thioesters
have large G of hydrolysis
PEP:
group transfer potential fromtautomerization
of enol to keto form(pyruvate to phospho
enolpyruvate)
is exergonic
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Other phosphorylated compounds & thioesters
have large G of hydrolysis
Hydrolysis of PEP followed by spontaneous
tautomerization Conversion provides energy to
phosphorylate ADP ATP
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Hydrolysis of PEP
1,3-bisphosphoglycerate:
contains anhydride bond between C-1 &phosphoric acid
Subject to resonance influences & solvation
effects Hydrolysis releases free energy
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Phosphocreatine:
P-N bond can be hydrolyzed to Pi &creatine
Release of Pi releases free energy, drivesreaction forward
Reaction used in extreme skeletal muscleexertion
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Hydrolysis of Phosphocreatine
Thioesters: have high G content
Do not release Pi
Have sulfur
Lack resonance stabilization
Have large G of hydrolysis
Greater than oxygen esters
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Acetyl Co-A
Under aerobic conditions the end product ofglycolysis:
pyruvic acid.
The next step :
the formation of acetyl coenzyme A (acetylCoA) which is the initiator of the citric acidcycle.
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Acetyl Co-A
In carbohydrate metabolism,
acetyl CoA:
the link between glycolysis and the citricacid cycle.
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Acetyl Co-A
The general pathway for the production ofacetyl CoA from sugars and fats.
The mitochondrion in eukaryotic cells: the place where acetyl CoA; produced from
both types of major food molecules.
It is the place: where most of the cell's oxidation reactionsoccur and where most of its ATP is made.
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In summary:
compounds with large, negative G0 ofhydrolysis give products that are morestable than reactants
This is because:
Bond strain due to repulsion is relieved byhydrolysis (ATP)
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ATP provides energyby group transfer, NOTby hydrolysis
Traditionally a reaction supplied by ATP iswritten:
ATP ADP + Pi
Glutamate + NH3 Glutamine
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ATP actually provides energyby group
transfer
Actual process is two steps:
Part of ATP transferred to someintermediate
covalently bonded phosphates
raises the free energy content
The moiety just transferred isdisplaced generates AMP or Pi
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ATP actually provides energyby group
transfer
Important exception: skeletal musclecontraction
Non-covalent binding of ATP
Hydrolysis to ADP & Pi
Provides energy to change protein
conformation
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ATP Hydrolysis: Two Steps
1.Transfer of phosphoryl group from ATP
to glutamate 2. Phosphoryl group displaced by NH3 and
released as Pi
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ATP actually provides energy
catabolism directed toward synthesis of
high-energyphosphate compounds puts energy into a compound
Energy can be metabolically transformed
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Assembly of macromolecules
Energy needed for:
condensation
sequencing
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Assembly of Macromolecules
For example:
In DNA, RNA, protein synthesis
breakdown of nucleoside triphosphate
coupled to endergonic process
Producing a specific polymer
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Other functions of ATP
ATP energizes active transport acrossmembranes
ATP supplies energy for muscle contraction Bioluminescence:
Firefly flashes:
Luciferin converted to light by luciferase
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Biological Oxidation-Reduction Reactions
Flow of electrons is responsible for mostwork done by living organisms
Source of e- is reduced compounds Metabolic pathways are complex, require
intermediate or e- carriers
Cells contain energy transducers convert e- flow into work
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Redox reactions may be described ashalf-reactions
Example: Oxidation of ferrous (Fe 2+) ionby cupric (Cu2+) ion:
Fe 2++ Cu 2+ Fe 3+ + Cu+
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Electrons transferred in one of four
ways:
Directly as e-
As hydrogen atoms
In the form of hydride ions (:H-)
With direct combination to oxygen
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Reducing Equivalent:
Typically, designates a single e- equivalent
May be e-, H, or (:H-)
May occur in rxn with O2 Participates in re-dox reaction
In biology, two e- equivalents passingfrom substrate to oxygen
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Reduction potentials measure affinity for
electrons
In a solution containing two conjugate
redox pairs, e- transfer may occurspontaneously
Tendency depends on the relative affinity of
the e- acceptor of each pair for e-
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Eo, the STANDARD REDUCTION
POTENTIAL measures this affinity Basic principle of this measurement:
e- will flow through a circuit
from the half-cell with lower Eo
to the half-cell with higher Eo
Half-cell with greatest affinity: assigned a+Eo (in volts)
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LITERATURE CITED
Devlin,T.M. Textbook of Biochemistry with ClinicalCorrelations,Fifth Edition,Wiley-Liss Publications,NewYork, USA, 2002.
Lehninger, A. Principles of Biochemistry, Secondedition, Worth Publishers Co., New York, USA, 1993.
Matthews, C.K. and van Holde, K.E., Biochemistry,Second edition, Benjamin / Cummings PublishingCompany Inc., San Francisco, 1996.
Segel, I.H. Biochemical Calculations, Second Edition,John Wiley and Sons, New York, 1976.