At this point, a molecule of glucose (a six-carbon compound) that enters the pathway has been converted to two molecules of glyceraldehyde-3-phosphate.
Glyceraldehyde-3-Phosphate IsConverted to Pyruvate At thispoint, a molecule of glucose (a six-carbon compound) that enters the pathwayhas been converted to two molecules of glyceraldehyde-3-phosphate. We have notseen any oxidation reactions yet, but now we shall encounter them. Keep in mindthat in the rest of the pathway two molecules of each of the three-carboncompounds take part in every reaction for each original glucose molecule.Figure 17.7 summarizes the second part of the pathway, which is often referredto as the payoff phase of glycolysis,since ATP is produced instead of used in this phase. Step 6. Glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate. Thisreaction, the characteristic reactionof glycolysis, should be looked at more closely. It involves the addition of aphosphate group to glyceraldehyde- 3-phosphate as well as an electron-transferreaction, from glyceraldehyde-3- phosphate to NAD+. We will simplifythe discussion by considering the two parts separately. The halfreaction of oxidation is that of an aldehyde to a carboxylic acid group, inwhich water can be considered to take part in the reaction. RCHO + H2O- > RCOOH + 2H+ + 2e– The halfreaction of reduction is that of NAD+ to NADH. NAD++ 2H+ + 2e– -> NADH + H+ Theoverall redox reaction is thus RCHO + HO + NAD+3 RCOOH + H+ + NADH in whichR indicates the portions of the molecule other than the aldehyde and carboxylicacid groups, respectively. The oxidation reaction is exergonic under standardconditions ( ∆G°' = –43.1 kJ mol–1 = –10.3 kcal mol–1),but oxidation is only part of the overall reaction. Thephosphate group that is linked to the carboxyl group does not form an ester,since an ester linkage requires an alcohol and an acid. Instead, the car-boxylic acid group and phosphoric acid form a mixed anhydride of two acids byloss of water, 3-Phosphoglycerate + Pi - > 1,3-bisphosphoglycerate + H2O inwhich the substances involved in the reaction are in the ionized formappropriate at pH 7. Note that ATP and ADP do not appear in the equation. Thesource of the phosphate group is phosphate ion itself, rather than ATP. Thephosphorylation reaction is endergonic under standard conditions ( ∆G°'= 49.3 kJ mol–1 = 11.8 kcal mol–1). Theoverall reaction, including electron transfer and phosphorylation, is Let’s show the two reactions that make up this reaction. Thestandard free-energy change for the overall reaction is the sum of the valuesfor the oxidation and phosphorylation reactions. The overall reaction is notfar from equilibrium, being only slightly endergonic. ∆G°' overall =∆G°'oxidation + ∆G°' phosphorylation = (–43.1kJ mol–1) + (49.3 kJ mol–1) = 6.2 kJmol–1 = 1.5 kcal mol–1 Thisvalue of the standard free-energy change is for the reaction of one mole ofglyceraldehyde-3-phosphate; the value must be multiplied by 2 to get the valuefor each mole of glucose ( ∆G°' =12.4 kJ mol–1 = 3.0 kcal mol–1). The G under cellular conditions is slightly negative (–1.29 kJ mol–1or –0.31 kcal mol–1) (Table 17.1). The enzyme that catalyzes theconversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate is glyceraldehyde-3-phosphatedehydrogenase. This enzyme is one of a class of similar enzymes, theNADH-linked dehydrogenases. The structures of a number of dehydrogenases ofthis type have been studied via X-ray crystallography. The overall structuresare not strikingly similar, but the structure of the binding site for NADH isquite similar in all these enzymes (Figure 17.8). (The oxidizing agent is NAD+;both oxidized and reduced forms of the coenzyme bind to the enzyme.) Oneportion of the binding site is specific for the nicotinamide ring, and oneportion is specific for the adenine ring. Themolecule of glyceraldehyde-3-phosphate dehydrogenase is a tetramer, consistingof four identical subunits. Each subunit binds one molecule of NAD+,and each subunit contains an essential cysteine residue. A thioester involvingthe cysteine residue is the key intermediate in this reaction. In thephosphoryla-tion step, the thioester acts as a high-energy intermediate. Phosphateion attacks the thioester, forming a mixed anhydride of the carboxylic andphosphoric acids, which is also a high-energy compound (Figure 17.9). Thiscompound is 1,3-bisphosphoglycerate,the product of the reaction. Production of ATP requires a high-energy compoundas starting material. The 1,3-bisphosphoglyceratefulfills this requirement and transfers a phosphate group to ADP in a highlyexergonic reaction (i.e., it has a high phosphate-group transfer potential). Step 7.The next step is one of the tworeactions in which ATP is produced byphosphorylation of ADP. Theenzyme that catalyzes this reaction is phosphoglyceratekinase. By now the term kinaseshould be familiar as the generic name for a class of ATP-dependentphosphate-group transfer enzymes. The most striking feature of the reaction hasto do with energetics of the phosphate-group transfer. In this step inglycolysis, a phosphate group is transferred from 1,3-bisphosphoglycerate to a molecule of ADP, producing ATP, the firstof two such reactions in the gly-colytic pathway. We already mentioned that1,3-bisphosphoglycerate can easilytransfer a phosphate group to other substances. Note that a substrate, namely1,3-bisphosphoglycerate, hastransferred a phosphate group to ADP. This trans-fer is typical of substrate-level phosphorylation. It isto be distinguished from oxidative phosphorylation, in which transfer ofphosphate groups is linked to electron-transfer reactions in which oxygen isthe ultimate electron acceptor. The only requirement for substrate-levelphosphor-ylation is that the standard free energy of the hydrolysis reaction ismore nega-tive than that for hydrolysis of the new phosphate compound beingformed. Recall that the standard free energy of hydrolysis of 1,3-bisphosphoglycerate is –49.3 kJ mol–1.We have already seen that the standard free energy of hydrolysis of ATP is–30.5 kJ mol–1, and we must change the sign of the free-energychange when the reverse reaction occurs: ADP + Pi+ H+ - > ATP + H2O ∆G°' = 30.5 kJ mol–1= 7.3 kcal mol–1 The netreaction is 1,3-bisphosphoglycerate + ADP - > 3-Phosphoglycerate+ ATP ∆G°' = –49.3 kJ mol–1+ 30.5 kJ mol–1=–18.8 kJ mol–1= –4.5 kcal mol–1 Twomolecules of ATP are produced by this reaction for each molecule of glucosethat enters the glycolytic pathway. In the earlier stages of the pathway, twomolecules of ATP were invested to produce fructose-1,6-bisphosphate, and now they have been recovered. At this point, thebalance of ATP use and pro-duction is exactly even. The next few reactions willbring about the production of two more molecules of ATP for each originalmolecule of glucose, leading to the net gain of two ATP molecules inglycolysis. Step 8.The phosphate group is transferredfrom carbon - > to carbon 2 of theglyceric acid backbone, setting the stagefor the reaction that follows. Theenzyme that catalyzes this reaction is phosphoglyceromutase. Step 9.The 2-phosphoglycerate molecule losesone molecule of water,producing phosphoenolpyruvate. This reaction does notinvolve electron transfer; it is a dehydration reaction. Enolase, the enzyme that catalyzes this reaction, requires Mg2+as a cofactor. The water molecule that is eliminated binds to Mg2+in the course of the reaction. Step 10.Phosphoenolpyruvate transfers itsphosphate group to ADP, pro-ducing ATP and pyruvate. Thedouble bond shifts to the oxygen on carbon 2 and a hydrogen shifts to carbon Phosphoenolpyruvateis a high-energy compound with a high phosphate-group transfer potential. Thefree energy of hydrolysis of this compound is more negative than that of ATP(–61.9 kJ mol–1 versus –30.5 kJ mol–1, or –14.8 kcal mol–1versus –7.3 kcal mol–1). The reaction that occurs in this step canbe considered to be the sum of the hydrolysis of phosphoenolpyruvate and thephosphorylation of ADP. This reaction is another example of substrate-levelphosphorylation. Phosphoenolpyruvate- > Pyruvate + Pi ∆G°' = –61.9 kJ mol–1= –14.8 kcal mol–1ADP+ Pi - > ATP ∆G°' = 30.5 kJ mol–1= 7.3 kcal mol–1 The netreaction is Phosphoenolpyruvate + ADP - > Pyruvate + ATP ∆G°' = –31.4 kJ mol–1= –7.5 kcal mol–1 Sincetwo moles of pyruvate are produced for each mole of glucose, twice as muchenergy is released for each mole of starting material. Pyruvate kinase is the enzyme that catalyzes this reaction.Like phospho-fructokinase, it is an allosteric enzyme consisting of foursubunits of two dif-ferent types (M and L), as we saw with phosphofructokinase.Pyruvate kinase is inhibited by ATP. The conversion of phosphoenolpyruvate topyruvate slows down when the cell has a high concentration of ATP—that is tosay, when the cell does not have a great need for energy in the form of ATP. One of the most important questions that we can ask about anymetabolic pathway is, at which points is control exercised? Pathways can be“shut down” if an organism has no immediate need for their products, whichsaves energy for the organism. In glycolysis, three reactions are controlpoints. The first is the reaction of glucose to glucose-6-phosphate, catalyzedby hexokinase; the second, which is the production of fructose-1,6-bisphosphate, is catalyzed byphosphofructokinase; and the last is the reaction of PEP to pyruvate, catalyzedby pyruvate kinase (Figure 17.10). It is frequently observed that control isexercised near the start and end of a pathway, as well as at points involvingkey intermediates such as fructose-1,6-bisphosphate.When we have learned more about the metabolism of carbohydrates, we can returnto the role of phosphofructokinase and fructose-1,6-bisphosphate in the regulation of several pathways of carbohydratemetabolism. In the final stages of glycolysis, two molecules of pyruvate areproduced for each molecule of glucose that entered the pathway. These reactions involve electron transfer (oxidation–reduction) andthe net production of two ATP for each glucose. There are three control points in the glycolytic pathway.
Whatreactions convert glyceraldehyde-3-phosphate to pyruvate?
Where are the control points inthe glycolytic pathway?
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Biochemistry: Glycolysis : Glyceraldehyde-3-Phosphate Is Converted to Pyruvate |