Question

The concept of energy charge is a very useful way to think about how ATP levels control pathway activity. Discuss the role of ATP in the glycolytic pathway (between glucose and pyruvate and/or lactate) with a focus on how energy charge would alter the pathway and how the pathway activity would alter energy charge. Include both general aspects and specific ATP use and generation.

Answer 1

The energy?yielding steps of glycolysis involve reactions of 3?carbon compounds to yield ATP and reducing equivalents as NADH. The first substrate for energy production is glyceraldehyde?3?phosphate, which reacts with ADP, inorganic phosphate, and NAD in a reaction catalyzed by the enzyme glyceraldehyde?3?phosphate dehydrogenase:

The reaction has several steps. In the first, a thiol carbon of the enzyme attacks the aldehyde carbon of glyceraldehyde?3?phosphate to make a thiohemiacetal intermediate. (Recall from organic chemistry that carbonyl carbons are electron?poor and therefore can bond with nucleophiles, including thiols from which the proton is removed.) Next, NAD accepts two electrons from the enzyme?bound glyceraldehyde?3?phosphate. The aldehyde of the substrate is oxidizedto the level of a carboxylic acid in this step. Inorganic phosphate then displaces the thiol group at the oxidized carbon (carbon 1 of glyceraldehyde?3?phosphate) to form 1,3?bisphosphoglycerate:

The next step is the transfer of phosphate from 1,3?bisphosphoglycerate to ADP, making ATP, catalyzed by phosphoglycerate kinase.

This phase of glycolysis brings the energy balance from glucose back to zero. Two ATP phosphates were invested in making fructose?1,6?bisphosphate and two are now returned, one from each of the 3?carbon units resulting from the aldolase reaction.

The next reaction is the isomerization of 3?phosphoglycerate to 2?phosphoglycerate, catalyzed by phosphoglycerate mutase:

The reaction is pulled to the right by further metabolism of 2?phosphoglycerate. First, the compound is dehydrated by the removal of the hydroxyl group on carbon 3 and a proton from carbon 2, leaving a double bond between carbons 2 and 3. The enzyme responsible for this step is a lyase, enolase:


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