Microsoft PowerPoint - Chapter-6

8/18/2019 Microsoft PowerPoint - Chapter-6

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13. Bioenergetics and Biochemical

Reaction Types

13.1 Bioener etics and Thermod namics 490

Chapter-6

13.2 Chemical Logic and Common Biochemical

Reactions 495

13.3 Phosphoryl Group Transfers and ATP 501

13.4 Biological Oxidation-Reduction Reactions 512


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PART II


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Why we need to study this part ?

Metabolism is a highly coordinated cellular activity in which manymultienzyme systems (metabolic pathways) cooperate to:

1. obtain chemical energy by capturing solar energy or degrading

energy rich nutrients from the environment;

2. convert nutrient molecules into the cell’s own characteristic

molecules, including precursors o macromolecules;

3. polymerize monomeric precursors into macromolecules: proteins,

nucleic acids, and polysaccharides;

4. synthesize and degrade biomolecules required for specialized

cellular functions, such as membrane lipids, intracellularmessengers, and pigments.


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Energy vs Carbon source

Types of

TrophsEnergy

source

Carbon

source

Microorganisms Plants Animals

Photo-

AutotrophUV light CO2 algae, cyanobacteria,

sulphur bacteria, .. X

Photo – UV light Organics Purple bacteria, green

Heterotroph ac er a…

Chemo–

Autotroph

Inogranics:

NH4+,

NO2-, H2S,

H2, Fe2+

CO2 Nitrification bacteria,Sulphur oxidative

bacteria, hydrogen

producing bacteria…

Chemo–

Heterotroph

Organics Organics Fermentative bacteria,Enterobacteria…

X


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Auto trophs - (such as photo-synthetic bacteria, green algae, and vascular plants) can

use carbon dioxide from the atmosphere as their sole source of carbon, from which they

construct all their carbon-containing biomolecules (see Fig. 1–5). Some autotrophic

organisms, such as cyanobacteria, can also use atmospheric nitrogen to generate all

their nitrogenous components.

Heterotrophs cannot use atmospheric carbon

dioxide and must obtain carbon from their

environment in the form of relatively complex

organic molecules such as glucose. Multicellular

animals and most microor anisms areheterotrophic,

In our biosphere, autotrophs and heterotrophs

live together in a vast, interdependent cycle in

which autotrophic organisms use atmospheric

carbon dioxide to build their organic biomolecules,

some of them generating oxygen from water inthe process. Heterotrophs in turn use the organic

products of autotrophs as nutrients and return

carbon dioxide to the atmosphere Interdependent Cycle


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Metabolism, the sum of all the chemical transformations taking place in a cell or

organism, occurs through a series of enzyme-catalyzed reactions that constitute

metabolic pathways. Each of the consecutive steps in a metabolic pathway bringsabout a specific, small chemical change, usually the removal, transfer, or addition of a

particular atom or functional group.

Metabolites are series of metabolic intermediates formed during conversion of the

precursor into a product.

Catabolism is the de radative hase of metabolism in which or anic nutrient molecules

Definitions

(carbohydrates, fats, and proteins) are converted into smaller, simpler end products

(such as lactic acid, CO2, NH3). Catabolic pathways release energy, some of which is

conserved in the formation of ATP and the electron carriers (NADH, NADPH, and

FADH2); the rest is lost as heat.

Anabolism, also called biosynthesis, small, simple precursors are built up into larger

and more complex molecules, including lipids, polysaccharides, proteins, and nucleic

acids. Anabolic reactions require an input of energy, generally in the form of the

phosphoryl group transfer potential of ATP and the reducing power of NADH, NADPH,

and FADH2.


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FIGURE 3 Energy relationships

between catabolic and anabolic

path ways.


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Three types of nonlinear metabolic pathways.

Anabolism

Catabolism


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13. Bioenergetics and Biochemical

Reaction Types

13.1 Bioener etics and Thermod namics 490 13.2 Chemical Logic and Common Biochemical

Reactions 495

13.3 Phosphoryl Group Transfers and ATP 501

13.4 Biological Oxidation-Reduction Reactions 512


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13.1 Bioenergetics and Thermodynamics

Bioenergetics is the quantitative study of energy transductions—changes of

one form of energy into an other—that occur in living cells, and of the nature

and function of the chemical processes underlying these transductions.

Biological Energy Transformations Obey the Laws of Thermodynamics

Gibbs f ree energy, G, expresses the amount of energy capable of doing work during

a reaction at constant temperature and pressure. When a reaction proceeds with the

release of free energy (that is, when the system changes so as to possess less free

energy), the free-energy change, G, when 0 is said to be ender on ic reactions.Enthalpy, H, is the heat content of the reacting system. It reflects the number and kinds

of chemical bonds in the reactants and products. When a chemical reaction releases

heat, it is said to be exothermic; the heat content of the products is less than that of the

reactants and H 0 when entropy increases and DH, as noted above, < 0 when heat is released by

the system to its surroundings DG


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Free energy change, G

When a reacting system is not equilibrium,the tendency to move toward

equilibrium represents a driving force,the magnitude of which can beexpressed as the free-energy changefor the reaction, G.

< 0: exergonic: release free energy

> 0: endergonic: require energy

Ea

, – transition state-

In biosystem: living cells andorganisms, however, are opensystems, exchanging both materialsand energy with their surroundings;

living systems are never at equilibriumwith their surroundings.

G

Notes:

Endogenic : action or object coming from inside

Exogenic : action or object coming from out side


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Standard (transformed) free-energy changes, G’o

KEY CONVENTION: For

convenience of calculations,

biochemists define a standard state

different from that used in

chemistry and physics: in the

biochemical standard state, [H+] is

[C]c[D]d

[A]a[B]bKeq=

DG’o

= -RT ln K’eq

0 10- M (pH 7.0) and [H2O] is 55.5M. For reactions that involve Mg+2

(which include most of those with

ATP as a reactant), [Mg2+] in

solution is commonly taken to be

constant at 1 mM.

condition: Temp. 25oC = 298K, 1 atm

(101.3 kPa), concentration of reactants

= 1 M. G’o : biochemical reaction does not

occur in 1 M concentration, thus it is

the “transformed” Go

.K’eq thus is the “transformed” Keq


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Actual Free-Energy Changes (

G ) Depend on Reactant

and Product Concentrations

aA + bB cC+ dDv1v2

DG =DG’o + RT ln[products]

[reactants]

R : gas constant = 8.315 J/mol or = 1.987 cal/mol

T : absolute temperature (Kenvin temp (Ko

) , 25o

C = 298o

K)


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Standard Free-Energy Changes Are Additive

In the case of two sequential chemical reactions, A B and B C, each

reaction has its own equilibrium constant and each has its characteristic

standard free energy change, DG’o 1 and DG’o 1.

For an example

The overall reaction is exergonic. In this case, energy stored in ATP is used to drive the

synthesis of glucose 6-phosphate, even though its formation from glucose and

inorganic phosphate (Pi) is endergonic.


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SUMMARY 13.1 Bioenergetics and Thermodynamics

1. Living cells constantly perform work. They require energy for maintainingtheir highly organized structures, synthesizing cellular components,

generating electric currents, and many other processes.

2. Bioenergetics is the quantitative study of energy relationships and energy

conversions in biological systems. Biological energy transformations obey

the laws of thermodynamics

3. All chemical reactions are influenced by two forces: the tendency to achieve

the most stable bonding state (for which enthalpy, H, is a useful expression)

and the tendency to achieve the highest degree of randomness, expressed

as entropy, S. The net driving force in a reaction is DG, the free-energy

change, which represents the net effect of these two factors: DG =D H-TDS.

4. The standard transformed free-energy change, DG’o

, is a physical constantthat is characteristic for a given reaction and can be calculated from the

equilibrium constant for the reaction: DG’o = RT ln K’eq.


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SUMMARY 13.1 Bioenergetics and Thermodynamics

5. The actual free-energy change, G, is a variable that depends on DG’o and on

the concentrations of reactants and products: G = G’o + RTln

([products]/[reactants]).

6. When G is large and negative, the reaction tends to go in the forward direction;

when DG is large and positive, the reaction tends to go in the reverse direction;

and when G = 0, the system is at equilibrium.

-.the reaction occurs. Free-energy changes are additive; the net chemical reaction

that results from successive reactions sharing a common intermediate has an

overall free-energy change that is the sum of the DG values for the individual

reactions.


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13.2 Chemical Logic and Common Biochemical Reactions

Cellular chemistry does not encompass every kind of reaction learned in a typical

organic chemistry course. Biological reactions are determined by (1) their relevance

to that particular metabolic system and (2) their rates.

Most of the reactions in living cells fall into one of general categories:

(1) reactions that make or break carbon–carbon bonds;

(2) internal rearrangements, isomerizations, and eliminations;

(3) free-radical reactions;

(4) group transfers;

ox a on-re uc ons.

Note that: the five reaction types are not mutually exclusive; for example, an

isomerization reaction may involve a free -radical intermediate.

Two basic chemical principles:

1) a covalent bond can be broken in two general ways: homolytic cleavage and

heterolytic cleavage;

2) biochemical reactions involve interactions: nucleophiles or electrophiles.


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FIGURE 13–1 Two mechanisms

for cleavage of a C—C or C—H

bond. In a homolytic cleavage,

each atom keeps one of the

bonding electrons, resulting in the

formation of carbon radicals(carbons having unpaired

electrons) or uncharged hydrogen

atoms. In a heterolytic cleavage,

one of the atoms retains both

bonding electrons. This can result

in the formation of carbanions,

carbocations, protons, or hydrideion.

Formation of a C C bond involves

the combination of a nucleophilic

carbanion and an electrophilic

carbocation. Carbanions and

carbocations are generally so

unstable that their formation as

reaction intermediates can be

energetically inaccessible even

with enzyme catalysts.

(Carbon –anion )

(Carbon –cation )


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A anion donates electrons A cation pulls electrons

FIGURE 13–2 Common

nucleophiles and electrophiles

in biochemical reactions.

Chemical reaction mechanisms,

which trace the formation and

breakage of covalent bonds, are

communicated with dots

and curved arrows, a convention

known informally as “electron

pushing.” A covalent bond

consists of a shared pair of

electrons. Non-

bonded electrons important to

the reaction mechanism are

designated

by dots (:). For movement of asingle electron (as in a free

radical reaction), a single-headed

(fishhook-type) arrow is used ( ).

Most reaction steps involve an

unshared electron pair.


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The carbon of a carbonyl group has a

partial positive charge due to the

electron-withdrawing property of the

carbonyl oxygen, and thus is an

electrophilic carbon.

FIGURE 13–3 Chemical properties of carbonyl groups.

(a) The carbon atom of a carbonyl group is an electrophi le by virtue of the electron

withdrawing capacity of the electro negative oxygen atom, which results in a

resonance hybrid structure in which the carbon has a partial positive charge. (

(b) Within a molecule, delocalization of electrons into a carbonyl group stabilizes acarbanion on an adjacent carbon, facilitating its formation.

(c) Imines function much like carbonyl groups in facilitating electron withdrawal.

(d) Carbonyl groups do not always function alone; their capacity as electron sinks often

is augmented by interaction with either a metal ion (Me2+, such as Mg2+) or a

general acid (HA)


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aldolase

synthesis of citrate in the

citric acid cycle (TCA)

converts a six-carbon

compound to two three-

carbon compounds in

glycolysis

For both the aldol condensation and the Claisen condensation, a carbanion servesas nucleophile and the carbon of a carbonyl group serves as electrophile. The carbanion

is stabilized in each case by another carbonyl at the adjoining carbon.

In the decarboxylation reaction, a carbanion is formed on the carbon shaded blue as

the CO2 leaves. The reaction would not occur at an appreciable rate without the

stabilizing effect of the carbonyl adjacent to the carbanion carbon.

FIGURE 13–4 Some

common reactions that

form and break C—C

bonds in biological

systems.


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Internal Rearrangements, Isomerizations, and Eliminations

FIGURE 13–5 Carbocations in

carbon–carbon bond

formation. In one of the earlysteps in cholesterol

biosynthesis, the enzyme prenyl

transferase catalyzes

condensation of isopentenyl

pyrophosphate and dimethylallyl

pyrop osp a e o orm geranypyrophosphate (see Fig. 21–36).

The reaction is initiated by

elimination of pyrophosphate

from the dimethylallyl

pyrophosphate to generate a

carbocation, stabilized byresonance with the adjacent

CPC bond.Polymeration


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Isomerization

Elimination

FIGURE 13–6 Isomerization and elimination reactions.

(a) The conversion of glucose 6-phosphate to fructose 6-phosphate, catalyzed byphosphohexose isomerase.

(b) The reaction proceeds through an enediol intermediate. B1 and B2 are ionizable

groups on the enzyme; they are capable of donating and accepting protons (acting as

general acids or general bases) as the reaction proceeds. Pink screens indicate

nucleophilic groups; blue, electrophilic.


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Free radical reactions

– ree ra ca – n a e ecar oxy a on reac on.

Groups transfer reactions


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FIGURE 13–8 Alternat ive ways of showing the structure of inorganic

orthophosphate (Pi) (a) In one (inadequate) representation, three oxygens are single-

bonded to phosphorus, and the fourth is double-bonded, allowing the four different

resonance structures shown here. (b) The resonance structures can be representedmore accurately by showing all four phosphorus–oxygen bonds with some double-bond

character; the hybrid orbitals so represented are arranged in a tetrahedron with P at its

center. (c) When a nucleophile Z (in this case, the —OH on C-6 of glucose) attacks ATP,

it displaces ADP (W). In this SN2 reaction, a pentacovalent intermediate (d) forms

transiently.


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FIGURE 13–10 An ox idation-

reduction reaction.

FIGURE 13–9 The oxidation states of

carbon in biomolecules. Each

compound is formed by oxidation of the

red carbon in the compound shown

immediately above. Carbon dioxide isthe most highly oxidized form of carbon

found in living systems.


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SUMMARY 13.2 Chemical Logic and Common Biochemical

Reactions

■ Living systems make use of a large number of chemical reactions that can be

classified into general types.

■ Carbonyl groups play a special role in reactions that form or cleave C C bonds.

Carbanion intermediates are common and are stabilized by adjacent carbonyl groups

or, less often, by imines or certain cofactors.

■ A re-distribution of electrons can produce internal rearrangements, isomerizations,

and eliminations. Such reactions include intramolecular oxidation-reduction, change in

cis-trans arrangement at a double bond, and transposition of double bonds.

■ Homolytic cleavage of covalent bonds to generate free radicals occurs in some

pathways, such as in certain isomerization, decarboxylation, reductase, and

rearrangement reactions.

■ Phosphoryl transfer reactions are an especially important type of group transfer in

cells, required for the activation of molecules for reactions that would otherwise be highlyunfavorable.

■ Oxidation-reduction reactions involve the loss or gain of electrons: one reactant

gains electrons and is reduced, while the other loses electrons and is oxidized.

Oxidation reactions generally release energy and are important in catabolism.


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13.3 Phosphoryl Group Transfers and ATP

ATP Donates Phosphoryl, Pyrophosphoryl,

and Adenylyl Groups

18O: isotope


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Free Energy from hydrolysis of ATP

+ H20

(-)30.5 kJ/mol

H+ và

a –b phosphoanhydride: 45.6 kJ/molg -b phosphoanhydride: 30.5 kJ/mol


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BPP

+ H20

+ Pi

Other compounds are energy rich

: Bis-phosphoglycerate

- . mo

Bis-phosphoglycerate


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+ H20

PEP: Phosphoenolpyruvate

+ Pi

Other compounds are energy rich

Phosphoenolpyruvate

- . mo


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FIGURE 13–19 Ranking of biological phosphate

compounds by standard free energies of hydrolysis.


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SUMMARY 13.3 Phosphoryl Group Transfers and ATP1. ATP is the chemical link between catabolism and anabolism. It is the energy

currency of the living cell. The exergonic conversion of ATP to ADP and Pi or to AMP

and PPi, is coupled to many endergonic reactions and processes.

2. Direct hydrolysis of ATP is the source of energy in some processes driven byconformational changes, but in general it is not ATP hydrolysis but the transfer of a

phosphoryl, pyrophosphoryl, or adenylyl group from ATP to a substrate or enzyme

that couples the energy of ATP breakdown to endergonic transformations of

substrates.

3. Through these group transfer reactions, ATP provides the energy for anabolic

, ,transport of molecules and ions across membranes against concentration gradients

and electrical potential gradients.

4. To maintain its high group transfer potential , ATP concentration must be held far

above the equilibrium concentration by energy-yielding reactions of catabolism.

5. Cells contain other metabolites with large, negative, free energies of hydrolysis,

including phosphoenolpyruvate, 1,3-bisphosphoglycerate, and phosphocreatine.These high-energy compounds, like ATP, have a high phosphoryl group transfer

potential. Thioesters also have high free energies of hydrolysis.

6. ■ Inorganic polyphosphate, present in all cells, may serve as a reservoir of

phosphoryl groups with high group transfer potential.


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1. Directly as electrons. For example, the Fe2"/Fe3"redox pair can transfer an

electron to the Cu"/Cu2" redox pair

2. As hydrogen atoms. Recall that a hydrogen atom consists of a proton (H")

and a single electron (e-). In this case we can write the general equation

13.4 Biological Oxidation-Reduct ion Reactions

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

NAD-linked dehydrogenases, described below

4. Through direct combination with oxygen. In this case, oxygen combines

with an organic reductant and is covalently incorporated in the product, as

in the oxidation of a hydrocarbon to an alcohol:


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NADH and NADPH act with dehydrogenases as soluble electron

carriers

FIGURE 13–24 NAD and NADP. (a) Nicotinamide adenine dinucleotide, NAD +, and its

phosphorylated analog NADP+ undergo reduction to NADH and NADPH, accepting a

hydride ion (two electrons and one proton) from an oxidizable substrate. The hydride ion

is added to either the front (the A side) or the back (the B side).


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FADH2


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SUMMARY 13.4 Biological Oxidation-Reduction Reactions

1. In many organisms, a central energy-conserving process is the stepwise oxidation of

glucose to CO2,in which some of the energy of oxidation is conserved in ATP as

electrons are passed to O2.2. Biological oxidation-reduction reactions can be described in terms of two half-

reactions, each with a characteristic standard reduction potential, E’o.

3. The standard free-energy change for an oxidation-reduction reaction is directly

proportional to the difference in standard reduction potentials of thetwo half-cells:

Go ' = -n J E’o

4. Many biological oxidation reactions are dehydrogenations in which one or two

hydrogen atoms (H+ + e-) are transferred from a substrate to a hydrogen acceptor .

Oxidation-reduction reactions in living cells involve specialized electron carriers.

5. NAD and NADP are the freely diffusible coenzymes of many dehydrogenases. Both

NAD+ and NADP + accept 02 electrons and 01 proton.

6. FAD and FMN, the flavin nucleotides, serve as tightly bound prosthetic groups offlavoproteins. They can accept either 01 or 02 electrons and 01 or 02 protons.

Flavoproteins also serve as light receptors in crytochromes and photolyases.


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Oxidative phosphorylation or ATP synthesis by ATPsynthase

driven by the protons motive force generated through the

electrons transport chain

F1

ATP synthase

(F-type: FoF1- ATPase)

Fo


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FIGURE 19–19 Chemiosmotic model. In this simple representation of the

chemiosmotic theory applied to mitochondria, electrons from NADH and other

oxidizable substrates pass through a chain of carriers arranged asymmetrically in theinner membrane. Electron flow is accompanied by proton transfer across the membrane,

producing both a chemical gradient ( pH) and an electrical gradient ( y). The inner

mitochondrial membrane is impermeable to protons; protons can reenter the matrix only

through proton-specific channels (Fo). The proton-motive force that drives protons back

into the matrix provides the energy for ATP synthesis, catalyzed by the F1Fo complex.

ATP synthase


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SUMMARY 19.2 ATP Synthesis

■ The flow of electrons through Complexes I, III, and IV results in pumping of protons

across the inner mitochondrial membrane, making the matrix alkaline relative to the

intermembrane space. This proton gradient provides the energy (the proton-motive

force) for ATP synthesis from ADP and Pi by FoF1- ATP synthase in the innermembrane.

■ ATP synthase carries out “rotational catalysis,” in which the flow of protons through Fo

causes each of three nucleotide-binding sites in F1 to cycle from (ADP + Pi)–bound to

ATP-bound to empty conformations.

■ ATP formation on the enzyme requires little energy; the role of the proton-motive force

.

■ The ratio of ATP synthesized per reduced to H2O (the P/O ratio) is about 2.5 when

electrons enter the respiratory chain at Complex I (NADH), and 1.5 when electrons enter

at ubiquinone. (FADH2)

■ Energy conserved in a proton gradient can drive solute transport uphill across a

membrane.

■ The inner mitochondrial membrane is impermeable to NADH and NAD+ but NADH

equivalents are moved from the cytosol to the matrix by either of two shuttles. NADH

equivalents moved in by the malate-aspartate shuttle enter the respiratory chain at

Complex I and yield a P/O ratio of 2.5; those moved in by the glycerol 3-phosphate

shuttle enter at ubiquinone and give a P/O ratio of 1.5.

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