B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 41
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We haveseen that the crucial question is whether the entropy change forthe universe is positive or negative when that reaction occurs.In our idealized system, the cell in a box, there are two separatecomponents to the entropy change of the universe—the entropychange for the system enclosed in the box and the entropychange for the surrounding “sea”—and both must be addedtogether before any prediction can be made. For example, it ispossible for a reaction to absorb heat and thereby decrease theentropy of the sea (ΔSsea < 0) and at the same time to causesuch a large degree of disordering inside the box (ΔSbox > 0)that the total ΔSuniverse = ΔSsea + ΔSbox is greater than 0.
In thiscase, the reaction will occur spontaneously, even though thesea gives up heat to the box during the reaction. An example ofsuch a reaction is the dissolving of sodium chloride in a beakercontaining water (the “box”), which is a spontaneous processeven though the temperature of the water drops as the saltgoes into solution.Chemists have found it useful to define a number of new“composite functions” that describe combinations of physicalproperties of a system. The properties that can be combinedinclude the temperature (T), pressure (P), volume (V), energy(E), and entropy (S).
The enthalpy (H) is one such compositefunction. But by far the most useful composite function forbiologists is the Gibbs free energy, G. It serves as an accountingdevice that allows one to deduce the entropy change of theuniverse resulting from a chemical reaction in the box, whileavoiding any separate consideration of the entropy change inthe sea. The definition of G isG = H _ TSwhere, for a box of volume V, H is the enthalpy described above(E + PV), T is the absolute temperature, and S is the entropy.Each of these quantities applies to the inside of the box only.
Thechange in free energy during a reaction in the box (the G of theproducts minus the G of the starting materials) is denoted as ΔGand, as we shall now demonstrate, it is a direct measure of theamount of disorder that is created in the universe when thereaction occurs.At constant temperature the change in free energy (ΔG)during a reaction equals ΔH _ TΔS. Remembering thatΔH = _h, the heat absorbed from the sea, we have_ΔG = _ΔH + TΔS_ΔG = h + TΔS, so _ΔG/T = h/T + ΔSBut h/T is equal to the entropy change of the sea (ΔSsea), andthe ΔS in the above equation is ΔSbox.
Therefore_ΔG/T = ΔSsea+ ΔSbox = ΔSuniverseWe conclude that the free-energy change is a direct measureof the entropy change of the universe. A reaction will proceedin the direction that causes the change in the free energy (ΔG)to be less than zero, because in this case there will be a positiveentropy change in the universe when the reaction occurs.For a complex set of coupled reactions involving manydifferent molecules, the total free-energy change can be computed simply by adding up the free energies of all the differentmolecular species after the reaction and comparing this valuewith the sum of free energies before the reaction; for commonsubstances the required free-energy values can be found frompublished tables.
In this way, one can predict the direction ofa reaction and thereby readily check the feasibility of anyproposed mechanism. Thus, for example, from the observedvalues for the magnitude of the electrochemical proton gradientacross the inner mitochondrial membrane and the ΔG for ATPhydrolysis inside the mitochondrion, one can be certain that ATPsynthase requires the passage of more than one proton for eachmolecule of ATP that it synthesizes.The value of ΔG for a reaction is a direct measure of how farthe reaction is from equilibrium.
The large negative value forATP hydrolysis in a cell merely reflects the fact that cells keepthe ATP hydrolysis reaction as much as 10 orders of magnitudeaway from equilibrium. If a reaction reaches equilibrium,ΔG = 0, the reaction then proceeds at precisely equal ratesin the forward and backward direction. For ATP hydrolysis,equilibrium is reached when the vast majority of the ATPhas been hydrolyzed, as occurs in a dead cell.104PANEL 2–8: Details of the 10 Steps of GlycolysisFor each step, the part of the molecule that undergoes a change is shadowed in blue,and the name of the enzyme that catalyzes the reaction is in a yellow box.Step 1Glucose isphosphorylated by ATP toform a sugar phosphate.The negative charge of thephosphate prevents passageof the sugarphosphate through theplasma membrane,trapping glucose insidethe cell.CH2OHCH2OOHO+OHATPHOOH+OH1CH2OHHCOHHOCHHCOHHHCOHH2345CH Ophosphoglucoseisomerase+COCHCOHCOH2HO345phosphofructokinaseP654OHOH2CCH2OOATPCH2OH1HO23OHOHP+HOADP+H+OHOHOHfructose 6-phosphatefructose 1,6-bisphosphateCH2OOPHOHOOHOH(ring form)COCHHCOHHCOHCH2OPCH2OaldolaseHOCCH2OOH+dihydroxyacetonephosphateOCHdihydroxyacetonephosphateHCCOHCH2OHPCPtriose phosphate isomeraseOOPH(open-chain form)CH2OHCHfructose 1,6-bisphosphateStep 5The otherproduct of step 4,dihydroxyacetonephosphate, isisomerized to formglyceraldehyde3-phosphate.P(ring form)CH2O P6(open-chain form)fructose 6-phosphatePCH2OHOHOOH2COHC1CH2OPOH2COHOOH2CH+glucose 6-phosphate26(open-chain form)glucose 6-phosphateStep 3The new hydroxylgroup on carbon 1 isPphosphorylated by ATP, inpreparation for the formationof two three-carbon sugarphosphates.
The entry of sugarsinto glycolysis is controlled atthis step, through regulationof the enzymephosphofructokinase.+ADPOHOHglucoseStep 2A readilyreversibleP6 CH2Orearrangement of5the chemicalOstructure(isomerization)41moves theOH2HOOH3carbonyl oxygenfrom carbon 1 tocarbon 2, forming aOHketose from analdose sugar.(ring form)(See Panel 2–3,pp. 70–71.)Step 4Thesix-carbon sugar iscleaved to producetwo three-carbonmolecules. Only theglyceraldehyde3-phosphate canproceed immediatelythrough glycolysis.POhexokinaseCOHCH2Oglyceraldehyde3-phosphatePglyceraldehyde3-phosphateP105Step 6The two moleculesHOof glyceraldehyde 3-phosphateare oxidized. TheC+energy-generation phase ofglycolysis begins, as NADH andH C OHa new high-energy anhydridelinkage to phosphate areCH2O Pformed (see Figure 13–5).glyceraldehyde 3-phosphateOOStep 7The transferto ADP of thehigh-energy phosphategroup that wasgenerated in step 6forms ATP.glyceraldehyde 3-phosphatedehydrogenaseOHCH2O3HCenolaseCPCH2OHOP+P+H2OCH2O–OCCOphosphoenolpyruvateO–OO–O2-phosphoglycerateStep 10 The transfer toADP of the high-energyphosphate group that wasgenerated in step 9 formsATP, completingglycolysis.PCH2OHCOO2-phosphoglycerateO–CCP3-phosphoglycerateHCphosphoglycerate mutaseCPO–OC2ADP+Cpyruvate kinaseH+COCH2CH3phosphoenolpyruvatepyruvate+ATPCCH2OHOHOO–ONET RESULT OF GLYCOLYSISCNADHOHATP3-phosphoglycerate1O+OHCH2OO–OO–CP1,3-bisphosphoglycerateStep 9The removal ofwater from 2-phosphoglyceratecreates a high-energy enolphosphate linkage.PCADPHHOHOphosphoglycerate kinaseOHStep 8The remainingphosphate ester linkage in3-phosphoglycerate,which has a relatively lowfree energy of hydrolysis,is moved from carbon 3to carbon 2 to form2-phosphoglycerate.C+ H+NADH1,3-bisphosphoglyceratePCH2O+CH2O+CPCPiHCH+NAD+OOATPCH3ATPOHO–OOHATPATPOCNADHATPATPCOCH3glucoseIn addition to the pyruvate, the net products aretwo molecules of ATP and two molecules of NADH.two moleculesof pyruvatePANEL 2–9: The Complete Citric Acid Cycle106+NAD+NADH + Hcoenzyme AOCH3 COverview of the complete citric acid cycle.The two carbons from acetyl CoA thatenter this turn of the cycle (shadowed inred ) will be converted to CO2 insubsequent turns of the cycle: it is the twocarbons shadowed in blue that areconverted to CO2 in this cycle.HS CoACOO–CO2pyruvateOacetyl CoA(2C)CH3 C S CoAnext cycleC OCH2COO–+NADH + HNAD+COO–COO–oxaloacetate (4C)H2OCOO–CH2HO C COO–Step 1Step 2CH2COO–COO–C OCH2COO–Step 8H C OHCH2 malate (4C)COO–HS CoACOO–HC COO–oxaloacetate (4C)HO CHCOO–CITRIC ACID CYCLENAD+Step 3H2Ofumarate (4C)Step 7isocitrate (6C)CH2citrate (6C)α-ketoglutarate (5C)COO–CHCHsuccinyl CoA (4C)succinate (4C)COO–Step 6COO–Step 5CH2CH2FADH2FADH2OCOO–GTPHS CoAGDP+PiNADH + HCH2CO2CH2Step 4C OCOO–CH2CH2NAD+C OCOO–+COO–S CoA+HS CoANADH + HCO2Details of these eight steps are shown below.
In this part of the panel, for each step, the part of the molecule that undergoesa change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box.Step 1After theenzyme removes a protonfrom the CH3 group onacetyl CoA, the negatively Ocharged CH2– forms abond to a carbonyl carbonof oxaloacetate. Thesubsequent loss byhydrolysis of the coenzymeA (HS–CoA) drives thereaction strongly forward.Step 2An isomerizationreaction, in which water isfirst removed and thenadded back, moves thehydroxyl group from onecarbon atom to its neighbor.COO–CS CoA+CH3COcitratesynthaseOCoxaloacetateCOO–HCHHOCCOO–HCHCOO–citrateCH2COO–CCOO–acetyl CoAaconitaseH2OCCOO–CH2COO–COO–COO–HHOCH2S-citryl-CoAintermediateH2OCOO–H2OCH2HOCH2S CoACHCCOO–CHCOO–cis-aconitate intermediate+ HS CoA + H+citrateH2OH2OCOO–HCHHCCOO–HOCHCOO–isocitrate107Step 3In the first offour oxidation steps in thecycle, the carbon carryingthe hydroxyl group isconverted to a carbonylgroup.
The immediateproduct is unstable, losingCO2 while still bound tothe enzyme.COO–isocitratedehydrogenaseCHHCCOO–HOCHHStep 5A phosphatemolecule from solutiondisplaces the CoA, forming ahigh-energy phosphatelinkage to succinate. Thisphosphate is then passed toGDP to form GTP. (In bacteriaand plants, ATP is formedinstead.)HHNAD+COO–+NADH + HisocitrateStep 4The α-ketoglutaratedehydrogenase complex closelyresembles the large enzymecomplex that converts pyruvateto acetyl CoA, the pyruvatedehydrogenase complex inFigure 13–10. It likewisecatalyzes an oxidation thatproduces NADH, CO2, and ahigh-energy thioester bond tocoenzyme A (CoA).COO–COO–CHHCHCCOO–HCHCOCOH+COO–α-ketoglutarateCOO–COO–HCHHCHCOα-ketoglutarate dehydrogenase complex+ HS CoANADH + HHHCHCOsuccinyl-CoA synthetaseH2OPiHCHHCHCOO–HHCHGTPGDPCOO–succinate dehydrogenaseCHFADCOO–fumarateCOO–fumaraseHCOO–HOCHHCHCOO–HOCHHCHCOO–H2OfumarateCOO–HCFADH2CmalateCCOO–succinateStep 8In the last of fouroxidation steps in the cycle, thecarbon carrying the hydroxylgroup is convertedto a carbonyl group,regenerating the oxaloacetateneeded for step 1.HsuccinateCOO–HHCHCOCOO–S CoACHsuccinyl-CoACOO–CCS CoACO2α-ketoglutarateHH+NAD+COO–COO–Step 7The addition ofwater to fumarate places ahydroxyl group next to acarbonyl carbon.COO–oxalosuccinate intermediatesuccinyl-CoAStep 6In the third oxidationstep in the cycle, FAD accepts twohydrogen atoms from succinate.CO2malateCOO–malate dehydrogenaseCOCH2NAD+NADH + H+COO–oxaloacetate+ HS CoA108Chapter 2: Cell Chemistry and BioenergeticsREFERENCESGeneralBerg JM, Tymoczko JL & Stryer L (2011) Biochemistry, 7th ed.
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