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PCAT Biological Processes: How ATP Is Made

  • by Allison Chae
  • Jul 09, 2018
  • Biological Processes, PCAT Blog

You need to know about ATP on the PCAT. Adenosine triphosphate, or ATP, constantly comes up in the PCAT Biological Processes section. The first thing that we usually learn about ATP is that it is the basic unit of cellular energy—in other words, ATP provides the energy that the cell needs to do its work. However, if we just look at the structure of ATP, as shown below, we might not immediately see why ATP works well as a source of energy.

The key to understanding why ATP is a good energy source has to do with the three phosphate groups that we see on the left side of the structure above. These are high-energy bonds, primarily because of all of the negatively charged oxygen atoms bunched up next to each other (remember that like charges repel), but also because breaking up ATP into adenosine diphosphate (ADP) and an inorganic phosphate group (Pi) is entropically favorable.

Thus, hydrolyzing ATP to form ADP and Pi is energetically favorable, and this energy can be used (through thermodynamic coupling) to make energetically unfavorable reactions happen in the cell. So far, so good—all of this is pretty standard material for the PCAT Biological Processes section. But this leads to a further question: how does ATP production happen in the first place? The short answer is through metabolic processes like glycolysis, the Krebs cycle, and oxidative phosphorylation—but taking a closer look at ATP production in particular can help tie these pieces of knowledge together and take your expertise to the next level for the Biological Processes section.

The Cycle Of Phosphorylation

If we liberate energy from ATP by removing a phosphate group to form ADP and Pi, then it makes sense that we reform ATP by re-adding the phosphate group. This simple cycle is shown below:

Where it gets complicated is that the condensation reaction that forms ATP is carried out through different mechanisms in different pathways. The terms “substrate-level phosphorylation” and “oxidative phosphorylation” are used to describe these different mechanisms. Although these terms sound intimidating—and can be defined unhelpfully in some textbooks—they can be broken down straightforwardly.

Oxidative Phosphorylation

Oxidative phosphorylation is often learned in conjunction with the electron transport chain, which can be a complex topic, but for the PCAT, we can keep it simple: oxidative phosphorylation is what happens when ATP synthase makes ATP. It’s also worth knowing that this takes place at the end of the electron transport chain, and that ATP synthase is embedded in the inner mitochondrial membrane.

Why, then, is this called “oxidative phosphorylation”? Simple: the term oxidative refers to the fact that the electron transport chain includes multiple oxidation/reduction reactions that generate the proton gradient between the intermembrane space and the mitochondrial matrix, thereby powering ATP synthase. In other words, oxidative phosphorylation uses an enzyme powered by redox reactions.

Substrate-Level Phosphorylation

If oxidative phosphorylation is ATP production through ATP synthase, then you can think of substrate-level phosphorylation as any other way that ATP is produced. In other words, whenever you see ATP (or GTP) being directly produced in a metabolic pathway, substrate-level phosphorylation is taking place.

Substrate-level phosphorylation can occur through the transfer of a phosphate group from a metabolic intermediate to ADP, as in the ATP-generating steps in the payoff phase in glycolysis. It can also occur if an inorganic phosphate group (Pi) is added to ADP (or GDP) to form ATP or GTP, as in the step in which GTP is produced during the Krebs cycle.

Summing Up

Catabolic metabolic pathways have the goal of producing ATP, which can occur either via ATP synthase at the end of the electron transport chain (oxidative phosphorylation) or through the addition of a phosphate group directly to ATP through some other enzyme (substrate-level phosphorylation).

Hopefully, this blog post has helped to demystify these terms and to improve your sense of how energy-generating pathways work, which is useful for tying together the tremendous amount of information that you must master for the PCAT Biological Processes section.

To further hone your skills, we encourage you to check out the various PCAT resources that Next Step offers, including our PCAT practice tests (one of which is free!), our online PCAT course, and last but not least, PCAT tutoring. We wish you the best of luck in your journey towards pharmacy school!

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