Every Intro Bio student can cite ATP as ‘the energy currency of the cell’… but what do we mean by that? And why does it play that role? These are important questions, and they deserve answers. And real ones, not invocation of the mystical ‘high energy bonds’.

Perusing Wiki for an image to link for ATP, I’m surprised to find how many directly imply that the ‘value’ is in the bond between two phosphates. I think suggesting that this is the case does a disservice to students’ ability to analyze and understand. We’ve taught them by now that bonds are simply shared pairs of electrons. Blaming the bond for the potential energy inevitably raises the question “Is it the electrons that are special? If not, what is it about the bond?”. No and nothing.

The funny thing is that if you project an image of ATP with the charges correctly attributed to the phosphates and simply ask the students ‘does this molecule look happy to you?’ [sometimes with follow on of ‘do all of those groups look like they’re comfortable next to each other?’] you can generally get a pretty raucous NO! It’s that simple. The phosphates don’t ‘want’ to be held in close apposition. Like charges repel, and these are glued in close proximity to one another.

All the phosphates want to be happy is to be set free from one another. And yep, it’s those pesky covalent bonds that stand in their way. The ‘high energy’ incorporated in the bonds is not about them; it’s about the difference between the presence of the bonds and their absence (this is a bit of sloppy shorthand in biology that Chemists have threatened me over; when a Chemist breaks a bond, they literally pull it apart and leave the halves unsatisfied. In biology, 99.9% of the time we’re actually talking about SUBSTITUTIONS–we hydrolyze ATP and essentially recombine a water with ATP to yield a phosphate and ADP… but no partial bonds or lone electrons). So our interest is in ‘before/after’ comparisons, much like when we’re calling hydrogen bonds ‘weak’ because  the alternative to making an H-bond with X is… to make one with water, which is generally nearby.

Students can thus simply look at ATP and directly ‘observe’ its potential energy–energy that can be converted to kinetic energy (a ‘fleeing’ phosphate) simply by setting a phosphate free. An upcoming post will cover a module on looking at an ATPase as an easy to understand concrete example of a straightforward chemical reaction enhanced by having a protein (enzyme) help out with the awkward parts. My lecture materials on ATP and walking through an ATPase as an explicit example of enzyme function can be found here.

I generally leave ATP at this point for a while, but I think it’s critical to return once the focus of the course becomes energetics itself. A key question is WHY is ATP the ‘energy currency’? The simplicity of the chemistry above is a piece of the answer–any enzyme that can enhance the ‘popping off’ of the phosphate has access to that delightful burst of energy. And since water alone can trigger the event, it’s an easy one to assist.

Once students get involved in ‘sugar harvesting’ via the Kreb’s/TCA/Citric acid cycle, we can pose an interesting question. Most textbooks quote a figure of something like 36-38 ATP yielded per total biological oxidation of glucose. So why do we use such a cheap currency for energy? The analogy I tend to make is to compare sugar to gold and ATP to credit cards. Sure, a lump of gold is worth a ton–but trying spending one to get a burger at MacDonald’s. ATP is ready cash. To ‘harvest’ glucose requires the TCA cycle and an entire mitochondrion. So every enzyme that needed an energetic boost to do its thing would have to be dragging its own personal mitochondrion!

Alas, despite this vivid presentation, I’ve regularly been able to get students to claim on exams that a molecule of ATP has more biologically accessible energy than one of glucose. That ‘energy currency’ litany is pretty deeply entrenched 🙁

Last thought: one of the (many) evidences in support of inferring an RNA-world at the Beginning of Life is the common occurrence of RNA or RNA-like molecules (look up histidine biosynthesis, for example). Obviously, having the cell’s energy currency be one of the building blocks of RNA is right up there.

Addendum

While the charge-charge apposition is readily understood and sufficient for Intro Bio (in my view), I’d be remiss not to point out that there are other contributors to the favorability of ‘breaking’ the bond and freeing the outermost phosphate. One of these is resonance–there are more drawable structures for the freed phosphate than bound. A second is good ole entropy–2 smaller pieces (ADP and Pi) is more disordered than one with everybody tied together.