B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 31

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ATP is synthesized in an energetically unfavorable phosphorylationreaction in which a phosphate group is added to ADP (adenosine diphosphate).When required, ATP gives up its energy packet through its energetically favorablehydrolysis to ADP and inorganic phosphate (Figure 2–33). The regenerated ADPis then available to be used for another round of the phosphorylation reaction thatforms ATP.The energetically favorable reaction of ATP hydrolysis is coupled to many otherwise unfavorable reactions through which other molecules are synthesized.Many of these coupled reactions involve the transfer of the terminal phosphate inATP to another molecule, as illustrated by the phosphorylation reaction in Figure2–34.As the most abundant activated carrier in cells, ATP is the principle energycurrency.

To give just two examples, it supplies energy for many of the pumpsthat transport substances into and out of the cell (discussed in Chapter 11), and itpowers the molecular motors that enable muscle cells to contract and nerve cellsto transport materials from one end of their long axons to another (discussed inChapter 16).Energy Stored in ATP Is Often Harnessed to Join Two MoleculesTogetherWe have previously discussed one way in which an energetically favorable reaction can be coupled to an energetically unfavorable reaction, X → Y, so as toenable it to occur. In that scheme, a second enzyme catalyzes the energeticallyfavorable reaction Y → Z, pulling all of the X to Y in the process.

But when therequired product is Y and not Z, this mechanism is not useful.Figure 2–33 The hydrolysis of ATP toADP and inorganic phosphate. The twooutermost phosphates in ATP are held tothe rest of the molecule by high-energyphosphoanhydride bonds and are readilytransferred. As indicated, water can beadded to ATP to form ADP and inorganicphosphate (Pi). Hydrolysis of the terminalphosphate of ATP yields between 46 and54 kJ/mole of usable energy, dependingon the intracellular conditions. The largenegative ΔG of this reaction arises fromseveral factors: release of the terminalphosphate group removes an unfavorablerepulsion between adjacent negativecharges, and the inorganic phosphate ion(Pi) released is stabilized by resonance andby favorable hydrogen-bond formation withwater.66Chapter 2: Cell Chemistry and Bioenergeticshydroxylgroup onanothermoleculeO__O_O_ADENINEO P O P O P O CH2OOOATPRIBOSEphosphoanhydridebondΔG < 0O_Figure 2–34 An example of a phosphatetransfer reaction.

Because an energyrich phosphoanhydride bond in ATPis converted to a phosphoester bond,this reaction is energetically favorable,having a large negative ΔG. Reactions ofthis type are involved in the synthesis ofphospholipids and in the initial steps ofreactions that catabolize sugars.HO C C_OO P O C C_OPHOSPHATE TRANSFER_ADENINE_+ O P O P O CH2OOOADPRIBOSEphosphoesterbondA typical biosynthetic reaction is one in which two molecules, A and B, arejoined together to produce A–B in the energetically unfavorable condensationreactionA–H + B–OH → A–B + H2OMBoC6m2.58/2.34There is an indirect pathwaythatallows A–H and B–OH to form A–B, in whicha coupling to ATP hydrolysis makes the reaction go.

Here, energy from ATP hydrolysis is first used to convert B–OH to a higher-energy intermediate compound,which then reacts directly with A–H to give A–B. The simplest possible mechanism involves the transfer of a phosphate from ATP to B–OH to make B–O–PO3, inwhich case the reaction pathway contains only two steps:1. B–OH + ATP → B–O–PO3 + ADP2. A–H + B–O–PO3 → A–B + PiNet result: B–OH + ATP + A–H → A–B + ADP + PiThe condensation reaction, which by itself is energetically unfavorable, is forcedto occur by being directly coupled to ATP hydrolysis in an enzyme-catalyzed reaction pathway (Figure 2–35A).A biosynthetic reaction of exactly this type synthesizes the amino acid glutamine (Figure 2–35B). We will see shortly that similar (but more complex) mechanisms are also used to produce nearly all of the large molecules of the cell.Figure 2–35 An example of anenergetically unfavorable biosyntheticreaction driven by ATP hydrolysis.

(A)Schematic illustration of the formation of A–Bin the condensation reaction described inthe text. (B) The biosynthesis of the commonamino acid glutamine from glutamic acid andammonia. Glutamic acid is first converted toa high-energy phosphorylated intermediate(corresponding to the compound B–O–PO3described in the text), which then reactswith ammonia (corresponding to A–H) toform glutamine.

In this example, both stepsoccur on the surface of the same enzyme,glutamine synthetase. The high-energybonds are shaded red; here, as elsewherethroughout the book, the symbol Pi =HPO42–, and a yellow “circled P” = PO32–.(B)POOCCH2CH2H3N+CHCOO–high-energy intermediate(A)PATPOBACTIVATIONSTEPBOHPiproducts ofATP hydrolysisACONDENSATIONSTEPBCONDENSATIONSTEPOCH2CH2+H3NCHNH2CCH2–COOglutamic acidAPiproducts ofATP hydrolysisCHADPADPOHOhigh-energy intermediateATPNH3ammoniaACTIVATIONSTEPCH2H3N+CHglutamineCOO–CATALYSIS AND THE USE OF ENERGY BY CELLS67NADH and NADPH Are Important Electron CarriersOther important activated carrier molecules participate in oxidation–reductionreactions and are commonly part of coupled reactions in cells.

These activatedcarriers are specialized to carry electrons held at a high energy level (sometimescalled “high-energy” electrons) and hydrogen atoms. The most important of theseelectron carriers are NAD+ (nicotinamide adenine dinucleotide) and the closelyrelated molecule NADP+ (nicotinamide adenine dinucleotide phosphate). Eachpicks up a “packet of energy” corresponding to two electrons plus a proton (H+),and they are thereby converted to NADH (reduced nicotinamide adenine dinucleotide) and NADPH (reduced nicotinamide adenine dinucleotide phosphate),respectively (Figure 2–36). These molecules can therefore be regarded as carriersof hydride ions (the H+ plus two electrons, or H–).Like ATP, NADPH is an activated carrier that participates in many importantbiosynthetic reactions that would otherwise be energetically unfavorable.

TheNADPH is produced according to the general scheme shown in Figure 2–36A.During a special set of energy-yielding catabolic reactions, two hydrogen atomsare removed from a substrate molecule. Both electrons but just one proton (that is,a hydride ion, H–) are added to the nicotinamide ring of NADP+ to form NADPH;the second proton (H+) is released into solution. This is a typical oxidation–reduction reaction, in which the substrate is oxidized and NADP+ is reduced.NADPH readily gives up the hydride ion it carries in a subsequent oxidation–reduction reaction, because the nicotinamide ring can achieve a morestable arrangement of electrons without it. In this subsequent reaction, whichFigure 2–36 NADPH, an important carrier of electrons.(A) NADPH is produced in reactions of the general type shown onthe left, in which two hydrogen atoms are removed from a substrate.The oxidized form of the carrier molecule, NADP+, receives onehydrogen atom plus an electron (a hydride ion); the proton (H+) fromthe other H atom is released into solution.

Because NADPH holdsits hydride ion in a high-energy linkage, the hydride ion can easilybe transferred to other molecules, as shown on the right. (B) and(C) The structures of NADP+ and NADPH. The part of the NADP+molecule known as the nicotinamide ring accepts the hydride ion,H–, forming NADPH. The molecules NAD+ and NADH are identical instructure to NADP+ and NADPH, respectively, except that they lackthe indicated phosphate group.(A)HCOHNADP+CONADPHCHCC+C+Hoxidation ofmolecule 1(B)Hreduction ofmolecule 2(C)NADP+HOreduced formH+NCNH2NOPRIBOSEORIBOSEH–ADENINEPADENINEPOOHCnicotinamideringPNADPHoxidized formORIBOSERIBOSEOOPPthis phosphate group is+missing in NAD and NADHNH268Chapter 2: Cell Chemistry and Bioenergeticsregenerates NADP+, it is the NADPH that is oxidized and the substrate that isreduced. The NADPH is an effective donor of its hydride ion to other molecules forthe same reason that ATP readily transfers a phosphate: in both cases the transferis accompanied by a large negative free-energy change.

One example of the use ofNADPH in biosynthesis is shown in Figure 2–37.The extra phosphate group on NADPH has no effect on the electron-transfer properties of NADPH compared with NADH, being far away from the regioninvolved in electron transfer (see Figure 2–36C). It does, however, give a moleculeof NADPH a slightly different shape from that of NADH, making it possible forNADPH and NADH to bind as substrates to completely different sets of enzymes.Thus, the two types of carriers are used to transfer electrons (or hydride ions)between two different sets of molecules.Why should there be this division of labor? The answer lies in the need toregulate two sets of electron-transfer reactions independently.

NADPH operateschiefly with enzymes that catalyze anabolic reactions, supplying the high-energyelectrons needed to synthesize energy-rich biological molecules. NADH, by contrast, has a special role as an intermediate in the catabolic system of reactions thatgenerate ATP through the oxidation of food molecules, as we will discuss shortly.The genesis of NADH from NAD+, and of NADPH from NADP+, occur by differentpathways and are independently regulated, so that the cell can adjust the supplyof electrons for these two contrasting purposes. Inside the cell the ratio of NAD+to NADH is kept high, whereas the ratio of NADP+ to NADPH is kept low. This provides plenty of NAD+ to act as an oxidizing agent and plenty of NADPH to act asa reducing agent (Figure 2–37B)—as required for their special roles in catabolismand anabolism, respectively.There Are Many Other Activated Carrier Molecules in CellsOther activated carriers also pick up and carry a chemical group in an easily transferred, high-energy linkage.

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