The formation of ATP during glycolysis provides a particularly clear demonstration of how enzymes couple energetically unfavorable reactions with favorable ones, thereby driving the many chemical reactions that make life possible. Two central reactions in glycolysis (steps 6 and 7) convert the three-carbon sugar intermediate glyceraldehyde 3-phosphate (an aldehyde) into 3-phosphoglycerate (a carboxylic acid; see Panel 2–8, pp. 104–105), thus oxidizing an aldehyde group to a carboxylic acid group. The overall reaction releases enough free energy to convert a molecule of ADP to ATP and to transfer two electrons (and a proton) from the aldehyde to NAD+ to form NADH, while still liberating enough heat to the environment to make the overall reaction energetically favorable (∆G° for the overall reaction is –12.5 kJ/mole).
Figure 2–48 outlines this remarkable feat of energy harvesting. The chemical reactions are precisely guided by two enzymes to which the sugar intermediates
A short-lived covalent bond is formed between glyceraldehyde 3-phosphate and the –SH group of a cysteine side chain of the enzyme glyceraldehyde 3-phosphate dehydrogenase. The enzyme also binds noncovalently to NAD+.
Glyceraldehyde 3-phosphate is oxidized as the enzyme removes a hydrogen atom (yellow) and transfers it, along with an electron, to NAD+, forming NADH (see Figure 2–37). Part of the energy + H+ released by the oxidation of the aldehyde is thus stored in NADH, and part is stored in the high- glyceraldehyde 3-phosphate to the CO enzyme.
A molecule of inorganic phosphatehigh-energy inorganic displaces the high-energy thioesterphosphate phosphate bond to create 1,3-bisphospho-glycerate, which contains a high-energy phosphate bond.
1,3-bisphosphoglycerate
The high-energy phosphate group is transferred to ADP to form ATP.
The oxidation of an aldehyde to a carboxylic acid releases energy, much of which is captured in the activated carriers ATP and NADH.
Figure 2–48 energy storage in steps 6 and 7 of glycolysis. (a) in step 6, the enzyme glyceraldehyde 3-phosphate dehydrogenase couples the energetically favorable oxidation of an aldehyde to the energetically unfavorable formation of a high-energy phosphate bond. at the same time, it enables energy to be stored in naDh. The formation of the high-energy phosphate bond is driven by the oxidation reaction, and the enzyme thereby acts like the “paddle wheel” coupler in figure 2–32B. in step 7, the newly formed high-energy phosphate bond in 1,3-bisphosphoglycerate is transferred to aDp, forming a molecule of aTp and leaving a free carboxylic acid group on the oxidized sugar. The part of the molecule that undergoes a change is shaded in blue; the rest of the molecule remains unchanged throughout all these reactions.
(B) summary of the overall chemical change produced by reactions 6 and 7.