Paper : 04 of carbohydrates

Module :18 Generation of ATP

Principal Investigator Dr.S.K.Khare, Professor IIT Delhi.

Paper Coordinator Dr. Ramesh Kothari, Professor UGC-CAS Department of Biosciences

Saurashtra University, Rajkot-5, Gujarat-INDIA

Content Reviewer Dr. S. P. Singh, Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

Dr. Ramesh Kothari, Professor Content Writer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

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Metabolism of Carbohydrates Generation of ATP

Description of Module Subject Name Biochemistry Paper Name 04 Metabolism of carbohydrates Module 18 Generation of ATP Name/Title

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Metabolism of Carbohydrates Biochemistry Generation of ATP

Bio chemical mechanisms of generating ATP In , ATP is generated by two fundamental different biochemical mechanisms:

1. Substrate level phosphorylation ,and

2. .

Substrate level phosphorylation

 In substrate level phosphorylation, ATP is formed from ADP by transfer of a high energy phosphate group from an intermediate of a fueling pathway.

 The following reaction serve as an example

 As a consequence of the removal of a molecule of water, the low- energy ester linkage of phosphate in 2- phosphoglyceric acid is converted to the high energy enol linkage in phosphoenol pyruvic acid.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 This high- energy linked phosphate can then then be transferred to ADP, the consequence of which is generation of a molecule of ATP.

Generation of ATP by Electron Transport

 In a number of different mode of microbial metabolisms including respiration and , ATP is generated by transporting electron through the chain of carrier molecules with fixed orientation in a cell membrane.

 Although the complexity and component of electron transport chain vary, they have a certain common features:

 The component of chain are carrier molecules capable to undergoing revercible oxidation and reduction ; each member of chain is capable being reduced by reacting with the carrier molecules that precedes it and oxidized by the carrier that follows it.

Primary carrier-Iox carrier-IIred carrier-IIIox reduced Electron acceptor donor

Oxidized carrier-Ired carrier-IIox carrier -IIIred terminal Donor e acceptor

Schematic representation of an eleelectron transport chain

 In any specific example of an electron transport chain, certain members transport atoms while other transport only electron.  The orientation of carrier in the cell membrane is such that hydrogen carriers transport in the direction toward the outside of the cell and electron carrier transport toward the inside.

 Thus, at each conjunction in the chain of a hydrogen carrier and an electron carrier, a proton is transported out of the cell.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 The cell membrane is otherwise impermeable to proton ; as consequence electron transport traps a portion of the chemical energy released by the net reaction of the chain in the form of gradient across the membrane of proton and electric charge.

 Such a gradient termed as proton motive force (Δp) is form of potential energy capable of doing work : it drives certain permease system that concentrate externally supplied substrate within the cell; it provides the energy for flagellar- mediated cell motility and its drives the energy requiring synthesis of ATP from ADP.

 The synthesis of ATP at the expense of protonmotive force is catalyzed by complex membrane bound enzyme , ATP phosphohydrolase ( some time termed as ATP ase )

composed in all bacterial studied , of two multicomponant protein BF0 and BF1.

 The subunit composition and membrane insertion of BF0 and BF1 are shown in figure.

 The α and β subunit of BF1are arranged alternately to form a hollow hexagon, the central hole of which contain the γ subunit associated with other subunit δ and ε.

 Thus BF1 probably has the subunit structure α3β3γδε .

 The α and β subunit form the catalytically active portion of structure ,the site where ATP is synthesized from ADP and inorganic phosphate ;the γ,δ and ε subunit form a proton translocating stalk and gate that bring to the active site at the proper rate the proton that drive reaction.

 The peptide form a proton channel through the membrane they are hihly hydrophobic accounting for their intra membrane location

 ATP phosphohydrolase catalyzed a reversible reaction .ATP can be synthesize at a expense of proton motive force ,or in certain case a proton motive force can be established at the expense of intracellular ATP.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

Schematic representation of the subunit composition and membrane insertation of ATP phosphohydrolase.

Value of E0’ for components in electron transport chains

 In order for an electron transport chain to function ,there must be a gradient of susceptibility to oxidation; i.e each component must be capable of being reduced by reduced form of previous component and oxidized by the oxidized form of the subsequent component in the chain.

 The relative susceptibility of a substance to oxidation or reduction can be described quantitatively in terms of its electrode potential or reduction potential ;this is the

relative voltage required to remove an electron from H2. Thus standard reduction potential is that of hydrogen electrode

+ - ½ H2 = H + e

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 Which is assigned an arbitrary value of 0.0 volts under standard condition . At the pH 7.0,near which most biological reaction occurs, the potential of hydrogen electrode is -0.42 V.

 The symbol E0’ designates electrode potentials measured under these condition .

 Knowing E0’ value of two half reaction , the free energy changed of a coupled reaction can be calculated from the relationship

ΔG’0 = nFΔE’0

 Where ΔG’0 is the free energy change at pH 7.0 ;n is the number of electron

transferred ;F is the faraday and ΔE’0 is the algebraic difference between the potential of the two half reaction.

 For example the reduction of oxygen by hydrogen as (H2 +1/2 O2H2O) can be divided in to two half reactions.

+ H2 =2H +2e- (ΔE’0 = -0.42V) and

H2O = 1/2 O2 + H2 + 2e- (ΔE’0 = +0.82V)

 The energy change can be calculated to be

ΔG’0 =-2 * 23,000 [0.82-(-0.42)] = 57,040 cal

 For a typical biology oxidation , for example , the oxygen- linked oxidation of NADH

(ΔE’0 = -0.32V), the analogous calculation shows a free energy change of -52,400 cal , not significantly different from that for oxidation of hydrogen.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 The carrier in an electron transport chain participate in a series of reaction of

increasing ΔE’0 values , between that of the primary electron donor and terminal electron acceptor.

 The position on the E’0 scale of several typical electron carrier ,primary electron donor, and terminal electron acceptor are shown in figure.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

The Componants of Electron Transport Chain

 The electron transport chain of aerobic chemoheterophs are the most thoroughly studied.

 Those involved in the oxidation of organic compound always contain four different classes of molecules.

 Two classes, the flavoprotein and quinines ,are hydrogen carrier; the others,the iron sulphur protein and cytochromes are electrone carriers.

 Flavoprotein have a yellow-colored prosthetic group derived biosynthetically from riboflavin (vitamin B12).

 The prosthetic group may be either flavin mononucleotide (FAD); both possess the same active site capable of undergoing reversible oxidation and reduction by donating or accepting two hydrogen atom respectively.

Structure of riboflavin 9

Metabolism of Carbohydrates Biochemistry Generation of ATP

 The flavo proteins are members of a large class and differ widely with respect to

their E’0 values.

 Some are active in the primary dehydrogenation of organic substrate (e.g succinate) ;other participate as hydrogen carriers within an electron transport chain; and still

other react directly with molecular oxygen with the formation of H2O2.

 Most electron transport chain contain either ubiquinone , a substituted benzoquinone, or menaquinone , a substituted nepthaquinone.

 The former occur most frequently in Garm negative bacteria and in the mitochondria of eukaryotes, and the latter most frequently in Gram positive bacteria.

 A few facultative anaerobes, including, E.Coli ,contain both quinines but tend to use ubiquinone for aerobic respiration .

 On reduction they accept two hydrogen atom to form the corresponding quinol.

A- Structure of ubiquinone

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Metabolism of Carbohydrates Biochemistry Generation of ATP

B-reversible reduction of a quinine to form a quinol

C- structure of menaquinone

 The iron sulfur protein contain two, four or eight atoms of labile sulfur, so called

because they are released as H2S by strong acids.

 The iron atoms in 2 Fe-S protein are held in a lattice composed of four atoms of cysteine sulfur and the two labile sulfur atoms.

 The iron atoms in the 4Fe-4S proteins interact with four labile sulfur atoms to form a cube that is held in place within the protein by four cysteine residue.

 The 8Fe-8S protein contain two active centers identical to those found in 4Fe-4S protein, thus enabling them to accept on reduction, two electrons while 2Fe-2S and 4Fe-4S protein can accept only one.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 The cytochromes belong to the class of heme protein, a class that also includes hemoglobin and catlase.

 All have one or more prosthetic groups derived from heme, a cyclic tetrapyrrole with an atom of iron chelated within the ring system.

Structure of heme

 Electron transfer by the cytochromes involves a reversible oxidation of this iron atom Fe 2+ =Fe3+ + e-

 In an analogous way to the oxidation of an iron atom in the iron –sulfur proteins.

 The cytochromes have characteristic absorption band in the redused state that permit recognition of the several different members of the class, which are designated by terminal latter (e.g.,cytochrome c).

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Metabolism of Carbohydrates Biochemistry Generation of ATP

The absorption spectrum of cytochrome -c

 There are four types of heme prosthetic groups known (a,b,c,and d) that differ principally in the nature of the substituent group at the periphery of the heme.

 Individual cytochromes contain one or more of these groups in various combinations.

 The molecular weights and reduction potentials of cytochromes vary widely.

 Cytochrome contentof bacteria is quite variable among species and environments.for example, an aerobically grown bacterium will have a different cytochrome composition from that of the same strain grown anaerobically or even grown with a restricted supply of oxygen.

 The presence of a c- type cytochrome in a particular bacterium is correlated with the outcome of anempirical procedure , the oxidase test,whichhas considarble , diagnostic importance in identification of aerobic bacteria.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 The test is performed by putting a small quantity of bacteria ona piece of filter paper soaked in a dye ; either dichlrophenol indophenols or N,N dimethyl-p-phenylene – diamine.

 These dyes which are colorless in the reduced form by oxidase –positive species(which lake a c-type cytochrome).

Arrangement of Electron Transport Chain in Membrane

 As stated bacteria are quite variable with respect to their cytochrome content ; they are also variable with respect to other constituents of electron transport chain.

 A proposal for the aerobic respiratory chain in Esherichia coli is shown in figure.

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Metabolism of Carbohydrates Biochemistry Generation of ATP

 NADH in the cytoplasm generated by a reaction in a fueling pathway transfers on the inner aspect of the membrane two atoms toa flavoprotein embeded within the membrane.

 On the outer aspect of the membrane the flavoprotein transfers two electrons to an iron sulfurprotein thereby releases them out side when it transfer twoelectron toa b- type cytochrome.

 Finally, the cytochrome b transfer its electrons to another cytochrome that is termed a cytochrome oxidase because it has the capacity to transfer electrons to molecular

oxygen in a reaction on the inner surface that has H2O as a product.

 It will be noted that for each pair of electron transported through the chain four protons are pumped out of the cell, thus creating a proton motive force that can be used to do cellular work , for example ATP synthesis ,through the membrane bound ATP phosphohydrolase .

 It will also be noted that composition of the chain varies with the avilibility of oxygen.

 When fully aerobic ,cytochrome b550 serve as terminal electron carrier and cytochrome o as the terminal oxidase.

 When the supply of oxygen is limited cytochrome b558 and d play the corresponding roles.

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Metabolism of Carbohydrates Biochemistry Generation of ATP