B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 32
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For example, coenzyme A carries a readily transferableoxidizing agentfor catabolism7-dehydrocholesterolNAD+NADHCNADP+NADPHCHOH(B)reducing agentfor anabolismNADPH + H+NADP+CHO(A)CHHHcholesterolFigure 2–37 NADPH as a reducing agent. (A) The final stage in the biosynthetic route leading tocholesterol. As in many other biosynthetic reactions, the reduction of the C=C bond is achieved bythe transfer of a hydride ion from the carrier molecule NADPH, plus a proton (H+) from the solution.(B) Keeping NADPH levels high and NADH levels low alters their affinities for electrons (seePanel 14–1, p.
765). This causes NADPH to be a much stronger electron donor (reducingagent) than NADH, and NAD+ therefore to be a much better electron acceptor (oxidizingagent) than NADP+, as indicated.MBoC6 m2.61/2.37CATALYSIS AND THE USE OF ENERGY BY CELLS69Figure 2–38 The structure of theimportant activated carrier moleculeacetyl CoA. A ball-and-stick model isshown above the structure. The sulfuratom (yellow) forms a thioester bond toacetate.
Because this is a high-energylinkage, releasing a large amount of freeenergy when it is hydrolyzed, the acetatemolecule can be readily transferred to othermolecules.acetylgroupnucleotideADENINEH3CH HO H HO HC S C C N C C C N C COH H HH H Hhigh-energybondCH3 HCOOC O P O P O CH2O–O–OH CH3 HRIBOSE–Oacetyl groupOP OO–coenzyme A (CoA)acetyl group in a thioester linkage, and in this activated form is known as acetylCoA (acetyl coenzyme A). Acetyl CoA (Figure 2–38) is used to add two carbonunits in the biosynthesis of larger molecules.In acetyl CoA, as in other carrier molecules, the transferable group makes upMBoC6 e3.36/2.39only a small part of the molecule.The rest consists of a large organic portion thatserves as a convenient “handle,” facilitating the recognition of the carrier molecule by specific enzymes.
As with acetyl CoA, this handle portion very often contains a nucleotide (usually adenosine), a curious fact that may be a relic from anearly stage of evolution. It is currently thought that the main catalysts for earlylife-forms—before DNA or proteins—were RNA molecules (or their close relatives), as described in Chapter 6. It is tempting to speculate that many of the carrier molecules that we find today originated in this earlier RNA world, where theirnucleotide portions could have been useful for binding them to RNA enzymes(ribozymes).Thus, ATP transfers phosphate, NADPH transfers electrons and hydrogen, andacetyl CoA transfers two-carbon acetyl groups. FADH2 (reduced flavin adeninedinucleotide) is used like NADH in electron and proton transfers (Figure 2–39).The reactions of other activated carrier molecules involve the transfer of a methyl,carboxyl, or glucose group for biosyntheses (Table 2–3).
These activated carriersFADH2(A)OHCH3CCCH3HCCHCCNNCCCNGroup carried in high-energy linkageATPPhosphateNADH, NADPH, FADH2Electrons and hydrogensAcetyl CoAAcetyl groupCarboxylated biotinCarboxyl groupS-AdenosylmethionineMethyl groupUridine diphosphate glucoseGlucoseCOHCH2HCOHHCOHHCOHH2C O P P O CH2 ADENINERIBOSETABLE 2–3 Some Activated Carrier Molecules Widely Used in MetabolismActivated carrierNH+2H(B)FAD2e–FADH2Figure 2–39 FADH2 is a carrier ofhydrogens and high-energy electrons,like NADH and NADPH. (A) Structure ofFADH2, with its hydrogen-carrying atomshighlighted in yellow. (B) The formation ofFADH2 from FAD.Chapter 2: Cell Chemistry and Bioenergetics70are generated in reactions that are coupled to ATP hydrolysis, as in the examplein Figure 2–40.
Therefore, the energy that enables their groups to be used for biosynthesis ultimately comes from the catabolic reactions that generate ATP. Similar processes occur in the synthesis of the very large molecules of the cell—thenucleic acids, proteins, and polysaccharides—that we discuss next.The Synthesis of Biological Polymers Is Driven by ATP HydrolysisAs discussed previously, the macromolecules of the cell constitute most of its drymass (see Figure 2–7).
These molecules are made from subunits (or monomers)that are linked together in a condensation reaction, in which the constituents of awater molecule (OH plus H) are removed from the two reactants. Consequently,the reverse reaction—the breakdown of all three types of polymers—occurs by theenzyme-catalyzed addition of water (hydrolysis). This hydrolysis reaction is energetically favorable, whereas the biosynthetic reactions require an energy input(see Figure 2–9).The nucleic acids (DNA and RNA), proteins, and polysaccharides are all polymers that are produced by the repeated addition of a monomer onto one end ofa growing chain. The synthesis reactions for these three types of macromoleculesare outlined in Figure 2–41.
As indicated, the condensation step in each casedepends on energy from nucleoside triphosphate hydrolysis. And yet, except forthe nucleic acids, there are no phosphate groups left in the final product molecules. How are the reactions that release the energy of ATP hydrolysis coupled topolymer synthesis?For each type of macromolecule, an enzyme-catalyzed pathway exists whichresembles that discussed previously for the synthesis of the amino acid glutamine(see Figure 2–35).
The principle is exactly the same, in that the –OH group that willCARBOXYL GROUP ACTIVATIONcarboxylatedbiotinOCNADPP P–OOOSADENINECH2high-energybondNHCH3ORIBOSEC OENZYMEATPP P POCH2OADENINEPiC–OpyruvateRIBOSEbiotinOO–SCOHbicarbonateHN–OCOCH2NHC OOENZYMEpyruvate carboxylaseOOC–OoxaloacetateCARBOXYL GROUP TRANSFERFigure 2–40 A carboxyl group-transfer reaction using an activated carrier molecule. Carboxylated biotin is used by the enzyme pyruvatecarboxylase to transfer a carboxyl group in the production of oxaloacetate, a molecule needed for the citric acid cycle.
The acceptor molecule forthis group-transfer reaction is pyruvate. Other enzymes use biotin, a B-complex vitamin, to transfer carboxyl groups to other acceptor molecules.Note that synthesis of carboxylated biotin requires energy that is derived from ATP—a general feature of many activated carriers.MBoC6 m2.63/2.40CATALYSIS AND THE USE OF ENERGY BY CELLS(A) POLYSACCHARIDES(B) NUCLEIC ACIDSglucoseglycogenCH2OHOCH2OHOCH2OHOOHOHOHOHHO71OHOCH2OHOOHOHOOHCH2AOORNACH2OHOOPOOCH2COOHH2OOHOHenergy from nucleosidetriphosphate hydrolysisO(C) PROTEINSOCCRNCHHHHONCOHHCROCnucleotideCH2CCRprotein_CH2OGGOHOHRNAOHOHenergy from nucleosidetriphosphate hydrolysisH2OO_OOHHOPOOPOHOamino acidRCOOOHO_OPOOHproteinOHO_OCH2OHOOHOglycogenHAOOHCH2OHOHOCH2energy from nucleosidetriphosphate hydrolysisH2OOOOHOHORONCCHHHNCHROCOHFigure 2–41 The synthesis of polysaccharides, proteins, and nucleic acids.
Synthesisof each kind of biological polymer involves the loss of water in a condensation reaction.Not shown is the consumption of high-energy nucleoside triphosphates that is required toactivate each monomer before its addition. In contrast, the reverse reaction—the breakdownof all three types of polymers—occurs by the simple addition of water (hydrolysis).be removed in the condensation reaction is first activated by becoming involvedin a high-energy linkage to a second molecule. However, the actual mechanismsused to link ATP hydrolysis to the synthesis of proteins and polysaccharides aremore complex than that used for glutamine synthesis, since a series of high-energy intermediates is required to generate the final high-energy bond that is broken during the condensation step (discussed in Chapter 6 for protein synthesis).Each activated carrier has limits in its ability to drive a biosynthetic reaction.MBoC6 m2.65/2.41The ∆G for the hydrolysis of ATP to ADP and inorganicphosphate (Pi) dependson the concentrations of all of the reactants, but under the usual conditions in acell it is between –46 and –54 kJ/mole.
In principle, this hydrolysis reaction coulddrive an unfavorable reaction with a ∆G of, perhaps, +40 kJ/mole, provided that asuitable reaction path is available. For some biosynthetic reactions, however, even–50 kJ/mole does not provide enough of a driving force. In these cases, the pathof ATP hydrolysis can be altered so that it initially produces AMP and pyrophosphate (PPi), which is itself then hydrolyzed in a subsequent step (Figure 2–42).The whole process makes available a total free-energy change of about –100 kJ/mole. An important type of biosynthetic reaction that is driven in this way is theChapter 2: Cell Chemistry and Bioenergetics72(A)(B)OOOADENINE_ATPO P O P O P O CH2__O_OORIBOSEH2Oadenosine triphosphate (ATP)H2OOOO_O P O P O__+_P Pi__OADENINEO P O CH2OO+AMPRIBOSEpyrophosphateH2Oadenosine monophosphate (AMP)H2OOO_O P OH+_O P OH__OOphosphatephosphate+PiPisynthesis of nucleic acids (polynucleotides) from nucleoside triphosphates, asillustrated on the right side of Figure 2–43.Note that the repetitive condensation reactions that produce macromoleculescan be oriented in one of two ways, giving rise to either the head polymerizationor the tail polymerization of monomers.
In so-called head polymerization, thereactive bond required for the condensation reaction is carried on the end of theMBoC6 m2.66/2.42base3P P P Osugarbase1OHhigh-energy intermediateP Osugar2 ATPP OP PiH2Obase3P OsugarOH2 ADPsugarOHpolynucleotidechain containingtwo nucleotides2 Piproducts ofATP hydrolysisbase2base1P OnucleosidemonophosphatesugarP Opolynucleotide chaincontaining three nucleotidesbase2sugarP Obase3sugarOHFigure 2–43 Synthesis of a polynucleotide, RNA or DNA, is a multistep process driven by ATPhydrolysis. In the first step, a nucleoside monophosphate is activated by the sequential transfer ofthe terminal phosphate groups from two ATP molecules.
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