Why the high energy bond in ATP isn’t very high

         Wavefunction had an interesting post about ATP and bond energies.  http://wavefunction.fieldofscience.com/2010/09/does-bond-cleavage-require-or-release.html.  Like most of his posts, it got me to thinking, particularly about a lot of the blarney written about ATP. 

       I was taught that ATP contains a ‘high energy’  phosphate bond.  This really isn’t correct.  ATP is used by the cell as ‘money’.  Some activities such as breaking down glucose  produce ATP (money) others such as making DNA consume ATP.  The analogy to money is fairly stong.  Money permits the exchange of the labor of farming for the groceries they produce.    ATP, like money, facilitates two very different societal (cellular) activities while looking like neither.

      When people talk about a high energy phosphate bond, they are not talking about the energy it takes to break the bond apart (which is what chemists mean by bond energy).  Rather they are talking about the energy released when water is added across the phosphate bond hydrolyzing it.  Obviously in this process more than a phosphate to oxygen bond is broken.  Water bonds are also broken and new bonds form.  

       What is actually meant by a high energy phosphate bond is a bond which, when hydrolyzed yields more than 25 kiloJoules (6 kiloCalories) of energy per mole.  When you consider that it takes more than 10 times that to break a carbon carbon bond (348 kiloJoules/mole) the energy released just isn’t that high (so the bonds in ATP are not well named).  For the cell, this turns out to be a very good thing.  Read on.

       Now for some chemistry. Energy is gained from hydrolysis of a phosphoanydride (P-O-P) bond, because the two phosphorus atoms must compete for the electrons on the bridging oxygen, while in a phosphate group considered alone, they don’t have to.  Energy is also gained because the electrostatic repulsion between the negatively charged oxygen groups of a phosphoanhydride is lost on hydrolysis.  In the physiologic pH range, ATP has 3 to 4 negative charges, whose mutual electrostatic repulsions are partially relieved by ATP hydrolysis. Any time 2 molecules are produced from 1, entropy increases, which also tends to drive the reaction forward. 

       Why do cells use phosphate and not something else?   Probably because phosphoanhydride bonds are stable.  Even though they release  energy when hydrolyzed, the activation energy to do so is rather high (I should have a figure, but I don’t).  Remember, it is the activation energy which determines how fast reactions take place, not the difference in energy between the initial and final products of the reaction.  Hydrogen and oxygen gases mixed together would be stable for longer than the life of the universe (unless a spark is present).  The activation energy is just too high at room temperature.

       There isn’t much ATP around.  The amount in a cell is typically only enough to supply its  energy needs for a minute or two.  It is continually being hydrolyzed and regenerated.  The half life of an ATP molecule varies from seconds to minutes.  An average person makes (and consumes) 3 pounds of ATP per hour.  This is just at rest.  More is made with exercise.  The body contains under .1 pound of ATP at any one time. 

       The reservoir of energy in cells is creatine phosphate, glycogen, fat, glucose etc. etc.  It isn’t the ATP.   The analogy to money continues to hold.  The reservoir of wealth in a country is far greater than the amount of money in circulation.

       Anaerobic breakdown of glucose to lactic acid releases 2 moles of ATP per mole of glucose broken down, while aerobic breakdown to carbon dioxide and water yields 38 moles.  They both have their uses. Anaerobic breakdown of glucose produces ATP much faster (up to 100 times faster) than aerobic breakdown.   As well as outstripping the blood supply, this may be another reason fast muscle (those contracting rapidly and used sports, music, etc.) uses anaerobic glycolysis.  Slow muscles (e.g. the ones holding us up by contracting all the time) use aerobic metabolism, meaning they have lots of mitochondria. Why mitochondria — because that’s where ATP synthase is found. In animals, fast muscle fibers and slow muscle fibers segregate into different muscles.  Red meat is red because it has lots of mitochondria (and mitochondria have lots of iron).    Humans have both types mixed up.

        [ Cell vol. 130 pp. 220 - 221 '07 ] ATP synthase makes ATP at rates over 100 molecules/second.   However  since every day we produce and consume about half our body weight in ATP [ Nature vol. 417 p. 25 '02 ] and there are only 24 x 60 x 60 = 86,400 seconds in a day and the molecular mass of ATP is 500 daltons — a single ATPase makes 86,400,000 ATPs per day 43,200,000,000 Daltons of mass a day.  It takes 6 * 10^23 daltons to make a gram.  So to make a gram of ATP a day there must be 10^13 ATPases in our body.  Half our body weight is 35,000 grams (for the legendary 70 kiloGram man) so we’re back up to 10^17 ATP synthases in our body to make this much ATP.

         Have you ever set a sugar cube on fire using a match?  It burns quite nicely.  One mole of glucose (180 grams) produces 3,000 kiloJoules/mole when completely oxidized to carbon dioxide and water (this is why sugars are called carbohydrates).  Aerobic metabolism of glucose produces 38 moles of ATP, which when hydrolyzed each produce 25 kiloJoules.   38 * 25 = 950 kiloJoules.  Not very efficient.  Each ATP is worth a rather piddling 25 kiloJoules.  That’s exactly  the point.  If we burned sugar with maximum efficiency, we’d ignite.  Getting 38 moles of ATP from a mole of glucose lets the body produce energy in various places on demand in bitesized pieces without burning up.  

        Even this is too much sometimes.  Red blood cells, sitting in the richest oxygen environment of all (arterial blood) use ANAEROBIC metabolism, despite its inefficiency.  Actaully they use anaerobic metabolism because of its inefficiency.  Like a drunk in a bar, they’d be destroyed if they used all that’s in front of them.

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Comments

  • Wavefunction  On September 28, 2010 at 8:40 am

    Nice summary. Another reason why ATP hydrolysis is favorable is the resulting stability of the anion by virtue of charge delocalization. As I have mentioned a couple of times before on this blog, if you haven’t read it yet I will very strongly recommend the late Frank Westheimer’s musings on why nature chose phosphates (PDF). In DNA for instance, the phosphodiester linkage provides the double benefit of being stable enough to nucleophilic attack by water (by virtue of the negative charge) without being too stable and unable to hydrolyze. Phosphates strike a nice balance. On a related minor side note, although ATP concentrations are indeed not too high in the cell, kinase inhibitor designers have to worry about them all the time since compared to the concentration of drugs in the cell (ideally nanomolar for potent effect), ATP is in a large excess (millimolar concentration) and the drug has to compete with this ATP-rich environment.

  • luysii  On September 28, 2010 at 9:02 am

    One of the first courses I took in grad school was from Westheimer, and, being a pack rat, I still have my notes. I’ll see if these considerations are back there.

    Thanks for the explanation for the high activation energy of phosphodiester hydrolysis. It also helps explain why DNA and RNA don’t fall apart despite the huge amounts of negative charge they contain.

  • Jim  On October 2, 2010 at 6:23 am

    Great post — and the why phosphates paper is one of my all time favorites. Still, I’m not sure about the entropy argument; as this is a hydrolysis are we not two molecules going to two? Unless, I suppose, we want to get fancy and start thinking about magnesium binding–does the lower affinity of ADP for Mg compared to ATP provide a decent driving force? I’d always assumed not but could easily be widely wrong…

  • Ame  On February 9, 2012 at 12:31 pm

    What is ΔH of ATP hydrolysis? Without use of enzymes or metals. There is bond breaking so there must be an energy barrier above which this reaction occurs however most (if not all) literature accounts for ΔG which I know is -3.5 and -61 for ATP and ADP hydrolysis. But I am more concern with ΔH.

  • luysii  On February 9, 2012 at 12:39 pm

    Don’t know but it’s probably not going to be as favorable as deltaG, because part of the negativity of deltaG is from the increase in entropy when one molecule (ATP) becomes 2 (ADP + Pi). Recall that an increase in entropy decreases deltaG because there is a -T*deltaS term in deltaG.

  • X  On July 31, 2012 at 4:31 am

    Not a chemist (I never even took Chemistry!), haven’t taken biology in years. I was an English Major. Having said this, I would like to ask/suggest the following:

    “Why do cells use phosphate and not something else?” Probably because Phosphates are consistently low for Oxidation states? Unlike Carbons which range. I figure, from and evolutionary view, the easier the bond is to oxidize – the more likely to be utilized by single-celled organisms?

    At least those are my ignorant thoughts on the matter. The easier it is to consolidate energy, the more capable you are of survival..

    Thoughts?

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