Double the ATP Yield

A Retro-Aldol Reaction in Glycolysis—Dividing Assets to Double the ATP Yield 

The cleavage reaction catalyzed by aldolase is a net retro-aldol reaction. Details of the mechanism are shown here, beginning at the left with fructose-1,6-bisphosphate. 

As we have seen with aldolase, imine and enamine functional groups have widespread roles in biological chemistry. Yet the functions of imines and enamines in biology are just as we would predict based on their native chemical reactivity. 

This result is not surprising, because we know that the equiUbrium for an aldol addition (the reverse of the reaction above) is not favorable when the enolate adds to a ketone. Bnt, as mentioned earlier, dehydration of an aldol addition product can draw the equilibrium forward. We shall discuss the dehydration of aldols next (Section 19.4C). 

The carbon-carbon bond cleavage step in a retro-aldol reaction involves, under basic conditions, a leaving group that is an enolate, or under acidic conditions, an enol. Write a mechanism for the retro-aldol reaction of 4-hydroxy-4-methyl-2-pentanone under basic conditions (shown above). 

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See "The Chemistry of... A Retro-Aldol Reaction in Glycolysis Dividing Assets to Double the ATP Yield" for an important biochemical application that increases the energy yield from glucose. 

Palmitic acid is 16 carbons long, with no double bonds, so it requires 7 oxidation spirals to be completely converted to acetyl-CoA. After 7 spirals, there are 7 FAD(2H), 7 NADH, and 8 acetyl-CoA. Each NADH yields 2.5 ATP, each FAD(2H) yields 1.5 ATP, and each acetyl-CoA yields 10 ATP as it is processed around the TCA cycle. This then yields 17.5 + 10.5 + 80.5 = 108 ATP. However, activation of palmitic acid to palmityl-CoA requires two high-energy bonds, so the net yield is 108 - 2, or 106 moles of ATP. 

Four rounds of [3 oxidation of a fatty acid with a trans-A ° double bond would yield a trans-A -enoyl CoA derivative. This compound is the natural intermediate formed by an acyl CoA dehydrogenase. It would be hydrated by enoyl CoA hydratase to form the L-3-hydroxyacyl CoA derivative. For the fatty acid with a cis-A double bond, four rounds of (3 oxidation would produce a ds-A double bond, which would not serve as a substrate for enoyl CoA hydratase. An isomerase would convert this bond into the trans-A configuration to allow subsequent metabolism. Since the double bond already exists in the fatty acids and does not arise from (3 oxidations, one less FADH2 would be formed. Consequently, approximately 1.5 fewer ATP would be produced for each pre-existing double bond. 

After 10 h, the second phase was characterised by a gradual increase in heat flow rate that was restored to its former value by 13 h (see Figure 35A) This was entirely due to anaerobic processes (Figure 35B). The carbon flux was found to be double the level in phase 1. This was presumably due to the much lower yield of ATP by such processes that would be dominated by the reduction of pyruvate to lactate in substrate phosphorylation, with the net synthesis of 2 mol ATP per mol Glc The increased glycolytic flux would result in a decreased pH as seen in Figure 35A. It was not possible of course to monitor the viability of the cells over the 20-h period but one would imagine that the accumulation of toxic lactate [53] would have a profound effect on the cells. Indirectly, this may be supposed from the fact that the heat flow rate during this phase was approximately at the same level as in phase 1, despite the fact that I5x more carbon is required to produce the same quantity of ATP as by oxidative phosphorylation. For the purpose of this speculation, the reliable number calculated by Beavis [62] for the stoichiometric yield of ATP per glc of 33 has been chosen, but there are many other values to be found in the literature (see Section 3.2.8). 

Exodeoxyribonuclease V [EC 3.1.11.5] catalyzes the exonucleolytic cleavage of double-stranded DNA in the presence of ATP, in either the 5 - to 3 - or the 3 - to 5 -direction to yield 5 -phosphooligonucleotides. Thus, this enzyme exhibits a DNA-dependent ATPase activity. 

A2-tran.v-isomer by enoyl-CoA isomerase (see fig. 18.6). With the double bond in the A2-tra s-configuration, /3 oxidation can resume. As with the oxidation of oleoyl-CoA, one less FADH2 and 1.5 fewer ATPs are produced in the oxidation of linoleoyl-CoA compared to stearoyl-CoA. In addition, one NADPH is required for the reduction of the dienoyl-CoA. Hence, in balancing the yield for complete oxidation of linoleoyl-CoA, one less NADH would be available to the respiratory chain and, therefore, 2.5 fewer ATPs would be produced. This is true since the two nucleotides can be interconverted ... 

An 18-carbon saturated fatty acid yields 120 ATP. For a monounsaturated fatty acid, the double bond eliminates the step that produces FADHg, so there would be 1.5 ATP less for oleic acid, or 118.5 ATP total. 

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