bio.lesson document 16

8/6/2019 bio.lesson document 16

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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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changes in chemical reactions: H: Enthalpy (heat content)

-H: exothermic

+H: endothermic

S: Entropy+S = entropy increase


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At constant temperature & pressure:

G = H - TS


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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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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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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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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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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.

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bio.lesson document 16