ch 14 biyoenerjetikler ve metabolizma yonca duman

8/3/2019 Ch 14 Biyoenerjetikler Ve Metabolizma Yonca Duman

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METABOLZMA

oklu enzim sistemlerinin (metabolik yollar)bulunduu yksek oranda dzenli hcresel aktivite.

1.Gne enerjisinden ya da evredeki enerjice zengin

besinleri paralayarak kimyasal enerji elde etmek,

2.Besin molekllerini, makromolekllerin nclleride (precursors) dahil olmak zere hcrenin kendi

karakteristik molekllerine dntrmek,

3.Momomerik ncl bileiklerin makromolekllerepolimerizasyonuyla proteinler, nkleik asitlerve

polisakkaritleri oluturmak,

4.zel hcresel ilevler iin membran lipidleri, hcreii haberciler (intracellular messengers), pigmentler

gibi biyomolekllerin sentezini ve ykmnsalamak.


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Metabolic pathways are irreversible,

Catabolic and anabolic pathwaysmust differ,

Every metabolic pathway has a first

committed step,

All metabolic pathways are regulated,

Metabolic pathways in eukaryoticcells occurs in cellular locations.


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Metabolizma

Kimyasal dnmlerin herbiri (metabolik yollar)

organizma iin ne yapar?

Herbir metabolik yol nasl alr?

Metabolik ollarn herbiri di er metabolik ollarla

hcrenin bymesi ve btnln muhafaza etmekzere gerekli enerji ve rnleri retmek iin nasl

ilikiye geer?

Yaamdaki dinamik yatkn durumunun (steady-state)

salanmas, metabolik enerji retimi ve tketiminin

dengelenmesi nasl ok katmanl birok reglasyon

mekanizmasyla gerekleir?


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Canl hcrelerdeki metabolik yollarda 5 genel

kimyasal reaksiyon tipi grlr:

Oksidasyon-Redksiyon reaksiyonlar,

C-C balarn oluturan ya da kran reaksiyonlar,

Molekl ii dzenlemeler, izomerizasyonlar veeliminasyonlar,

Grup transferi reaksiyonlar,

Serbest radikal reaksiyonlar.


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Metabolik reaksiyonlarn oluumunda

iki temel unsur gz nnde tutulmal:

Kovalent ba oluumu ya da krlmas,

Birok biyokimyasal reaksiyondankleofil(elektronca zengin fonksiyonel

grup) ve elektrofil(elektronca fakir

fonksiyonel grup) gruplar arasndakietkileimler.


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Models of CH bond breaking.


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Biologically important nucleophilic and electrophilic groups.

(a) Nucleophiles.


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Biologically important nucleophilic and electrophilic groups.

(b) Electrophiles.


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1. Oxidation-reduction Reactions


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Farkl metabolik yollarda yer alan

ayn tip reaksiyonlar ayn genel

mekanizma ile ve ayn koenzimlerikullanarak gerekleirler.


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2. Group-transfer reactions

(a) Acyl group transfer


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(b) Phosphoryl group transfer


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The phosphoryl-transfer reaction catalyzed by hexokinase.


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(c) Glycosyl group transfer


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3. Reactions that make or break carbon-carbon bonds

Examples of CC bond formation and cleavage reactions.

(a) Aldol condensation.


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(b) Claisen condensation ester.


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(c) Decarboxylation of a -keto acid.


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Carbanion Stabilisation

(a) Carbanions adjacent to carbonyl groups are stabilized

by the formation of enolates.


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(b) Carbanions adjacent to carbonyl groups hydrogen

bonded to general acids are stabilized electrostatically or by

charge neutralization.


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(c) Carbanions adjacent to protonated imines (Schiff

bases) are stabilized by the formation of enamines.


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(d) Metal ions stabilize carbanions adjacent to carbonyl

groups by the electrostatic stabilization of the enolate.


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4. Eliminations, Isomerisations, and Rearrangements

Possible elimination reaction mechanisms using

dehydration as an example.


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Possible elimination reaction mechanisms using

dehydration as an example.


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Mechanism of aldoseketose isomerization.


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Rearrangements produce altered carbon skeletons


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Bioenergetics is the

quantitative study of the

energy transductions that

occur in living cells and of

the nature and function ofthe chemical processes

underlying these

transductions.


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G = H - T S

G G0 Reaction endergonic

G=0 Reaction in equilibrium

H H0 Reaction endothermic

S


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The second law of thermodynamicsstates that the entropy of the universe

increases during all chemical andphysical processes, but it does notrequire that the entropy increase takeplace in the reacting system itself.

Living Cells

The order produced within cells They create disorder in their

as they grow and divide is more surroundings in the coursethan compensated for by the of growth and division.disorder.

In short, living organisms Returning to their surroundingspreserve their internal order an equal amount of energyby taking from the surroundings as heat and entropy.free energy in the form ofnutrients o r sunlight.


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Kimyada Standart Koullar298 K = 25C

[A] = [B] = [C] = [D] = 1 M

G =G


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[H+] = 1 M pH = 0

Hcre ii pH 7

Biyokimyada Standart Koullar

[H+] = 10-7 M

[H2O] = 55.5 M[Mg+2] = 1 mM


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nsan eritrositlerinde [ATP] = 2.25 mM, [ADP] = 0.25 mM,[Pi] = 1.65 mM, pH = 7 ve Scaklk = 25C olan koullarda

ATP hidrolizinin gerek serbest enerji deiimi:


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Byk negatif G deerleri olan hidroliz reaksiyonlarnda rnler

reaktantlardan daha stabildir. Bunun nedenleri:

1. Reaktantlarda elektrostatik etkileimlerden kaynaklanan ba gerilmeleriyk ayrlmasyla rahatlar (ATP de olduu gibi),

2. rnler iyonize olarak stabilize olur (ATP, ail fosfatlar ve tiyoesterlerdeo u u g ,

3. rnler izomerizasyon (tautomerizasyon) ile stabilize olur(fosfoenolpirvatta olduu gibi),

4. rnler rezonansla stabilize olur (fosfokreatinden kreatin kmas,ailfosfatlar ve tiyoesterlerden karboksilat iyonu kmas, anhidrit ve esterbalarndan Pi kmas)


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G (kJ/mol)(1) PEP + H2O Pyruvate + Pi 61.9

i 2 .

Sum: PEP + ADP Pyruvate + ATP 31.4


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ATP ADP + Pi (- hidrolizi) G= 30.5 kJ/mo

- .inorganic pyrophosphatase

i iPP 2P G

= 19.2 kJ/mo


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G (kJ/mol)Palmitate + ATP Palmitoyl-adenylate + PPi 45.6

PPi 2Pi 19.2

a m toy -a eny ate + o a m toy - o + + .

Palmitate + ATP + CoASH Palmitoyl- CoA + AMP + 2Pi 33.4


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+2

Nucleoside diphosphatekinase

MgATP + NDP (or dNDP) ADP + NTP (or dNTP) G 0

High [ATP]/[ADP] ratio in the cells normally drives reaction to the right with

the net formation of NTPs or dNTPs.


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Transphosphorylations between nucleotidesoccur in all cell types

Ping-Pong mechanism of nucleoside diphosphate kinase


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Vigorously contarcted muscle consumes ATP produce ADP. Atp requirement of

muscle replenished by the following reactions:

+2

Adenylate kinase

Mg2ADP ATP + AMP G 0

ATPcontracted

+2

rea ne nase

MgPCr + ADP Cr + ATP G 12.5 kJ/mol

When a sudden demand for energy depletes ATP, the PCr reservoir is used to

replenish ATP at a rate considerably faster than ATP can be synthesized by

catabolic pathways.

At pH 7 and 2 mM Mg+2, ATP exists in the forms

-4 -3 -2 -


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ATP , HATP , H2ATP , MgHATP , and Mg2ATP

In thinking about the biological role of ATP, we write its hydrolysis as the biochemicalequation

ATP + H20 ADP + Pi [ ][ ]

[ ]o ieq

ADP PK = ATP

The corresponding apparent equilibrium constant depends on the pH and the concentration o

O

free Mg+ . Note that H+ and Mg+ do not appear in the biochemical equation because they areheld constant. Thus a biochemical equation does not balance.

At a pH above 8.5 in the absence of Mg+2 the chemical reaction is represented by

ATP

-4

+ H20

ADP

-3

+

-2

4HPO + H

+

-3 -2 +

4o

eq -4

ADP HPO H

K = ATP

The corresponding equilibrium constant depends only on temperature, pressure, and ionicstrength.

O

Biological


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Oxidation-Reduction

Reactions

Theflow of electronscan dobiological workin living systems.

+2 +2 +3 +

Oxidations-reductions can be described as half-reactions


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+2 +3

+2 +

Fe + Cu Fe + Cu(1) Fe Fe + e

(2) Cu + e Cu

Electron-donating molecule Reducing agent or Reductant

-

-

Electron-accepting molecule Oxidizing agent or Oxid

+2 +3

+

ant

Electron donor e + Electron acceptor

Fe Fe Conjugate reductant-oxidant pair ( redox pair)

Proton donor H + Proton acceptor

Proton donor / Proton acceptor Co

-

/

njugate acid-base pair


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+22 2

2

R-CHO + 4OH + 2Cu R-COOH + Cu + 2H(1) R-CHO + 2OH R-COOH + 2e + H

-

- -O O

O

Oxidation of a reducing sugar (adehyde or ketone) by cupric ion

+2 2

+2

(2) 2Cu + 2e + 2OH Cu + H

Reducing agent: R-CHO

Oxidizing agent: Cu

- - O O


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Electrons are transferred from one molecule (electron donor) to another (electron

acceptor) in one of four different ways:

1. Directly as electrons. For example, the Fe+2/Fe+3 redox pair can transfer an electron toh C +/C +2 d i


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the Cu+/Cu+2 redox pair:

Fe+2 + Cu+2 Fe+3 +Cu+

2. As hydrogen atoms. Recall that a hydrogen atom consists of a proton (H+) and a singleelectron (e-). In this case we can write the general equation:

AH2A+ 2e-+ 2H+

where AH2 is the hydrogen/electron donor. AH2 and A together constitute a conjugate, ,

transfer of hydrogen atoms:

AH2 + B A+BH2

3. As a hydride ion (:H-), which has two electrons. This occurs in the case of NAD-linked dehydrogenases.

4.

Through direct combination with oxygen. In this case, oxygen combines with anorganic reductant and is covalently incorporated in the product, as in the oxidation of ahydrocarbon to an alcohol:

R-CH3 + O2 R-CH2-OH

The hydrocarbon is the electron donor and the oxygen atom is the electron acceptor.


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[ ]l t tlRTE E +

Nernst Equation for Reduction Potential


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[ ][ ]electron acceptor

electron donor

Reduction potential (V)

Standard reduction potential (V)

Gas constant (8.315 J/mol K)

ln

:

:

:

RTE EnF

E

E

R

= +

Absolute temperature (K)

Faraday constant (96480 J/V mol)

T

:

:

:

T

F

n

[ ]

[ ]

he number of electrons transferred per molecule

298K (25 C)

electron acceptor0.026V

electron donorln

T

E En

=

= +


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The energy made available by a spontaneous electron flow

(the free-energy change for the oxidation-reduction reaction) is proportional to E:


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(the free-energy change for the oxidation-reduction reaction) is proportional to E:

G = -nFE or G' = -nF E'

CH3CHO + NADH+

+ H+ CH3CH2OH + NAD

+

(1) CH3CHO + 2H+

+ 2e- CH3CH2OH E' = -0.197 V

2 NAD+

+ 2H+

+ 2e- NADH + H+

E' = -0.320 V

E' = E'(Acceptor) - E'(Donor)

E' = -0.197 (-0.320) = 0.123 V

n = 2

G' = -2(96.5 kJ/Vmol)(0.123 V) = -23.7 kJ/mol

pH:7.0 & [Acetaldehyde] = [Ethanol] = [NAD+] = [NADH] = 1 M

[ ]AcetaldehydeRT

[Acetaldehyde]=[NADH]=1 M , [Ethanol]=[NADH]=0.1 M


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[ ]

[ ]acetaldehyde

acetaldehyde

+

NADH

AcetaldehydeEthanol

0.026 V 1.00.197 + = 0.167 V

2 0.1NAD

ln

ln

ln

RTE E

nF

E

RTE E

= +

=

= +

NADH

0.026 V 0.10.320 0.350 V2 1.0

0.167 V ( 0.350 V) 0.183 V

2

lnE

E

G nF E

G

= + =

= =

=

= 96.5 kJ/mol 0.183 V

35.3 kJ/molG

=

G = nFE


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The complete oxidation of glucose:

6 12 6 + 2 2 + 2 = - , mo2

Universal electron carriers

NAD+ Water soluble coenzymes that undergo reversible

NADP+ oxidation and reduction in many of the electron-FMN


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NADP oxidation and reduction in many of the electron FMNtransfer reactions of metabolism

FAD

NAD+

move readily from one enzyme to anotherNADP+

,FAD flavoproteins for which they serve as prosthetic

groups

Ubiquinone electron carriers and proton donors in thePlastoquinone nonaqueous environment of membranes

Fe-S proteins tightly bound prosthetic groups that undergoCytochromes reversible oxidation and reduction, also serve as

electron carriers in many oxidation-reductionreactions


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NAD+ + 2e- + 2H+ NADH + H+

NADP+ + 2e- + 2H+ NADPH + H+


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In most tissues [NAD+

+ NADH] 10-5

M

[NADP+

+ NADPH] 10-6

M

In many cells and tissues [NAD+

]/[NADH] is high, favoring hydride (:H-

)transfer from asubstrate to NAD

+to form NADH

[NADPH]/[NADP+] is high favoring hydride transfer from

NADPH to a substrate.

NAD+ generally functions in oxidations-usually as part

of a catabolic reaction,

NADPH is the usual coenzyme in reductions-nearly

always as part of an anabolic reaction.


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More than 200 enzymes are known to catalyze reactions in which NAD + (or NADP+) acceptsa hydride ion from a reduced substrate, or NADPH (or NADH) donates a hydride ion to anoxidized substrate.

The general reactions are

AH2 + NAD+ A + NADH + H+

+ + 2 +

where AH2 is the reduced substrate and A the oxidized substrate.

The general name for an enzyme of this type is oxidoreductase; they are also commonlycalled dehydrogenases.

Alcohol dehydrogenase+ +3 2 3CH CH OH + NAD CH CHO + NADH + H


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The association between a dehydrogenase enzymes and NAD or NADP is relatively loose;

the coenzyme readily diffuses from one enzyme to another

Glyceraldehyde-3-P dehydrogenase+ +(1) Glyceraldehyde-3-P + NAD 3-P-Glycerate + NADH + H

Alcohol dehydrogenase+ +(2) Acetaldehyde + NADH + H Ethanol + NAD

(T) Glyceraldehyde-3-P

+ Acetaldehyde 3-P-Glycerate + Ethanol

In the overall reaction there is no net production or consumption of NAD+ or NADHNo net change in the [NAD+ + NADH]


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FAD + 2e- + 2H+ FADH2FMN + 2e- + 2H+ FMNH2

ch 14 biyoenerjetikler ve metabolizma yonca duman

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