My thesis-writing has been powered by “turning over” hundreds of pounds of ATP a day! So here’s a review of ATP, and how it can serve as cellular “energy currency” – and thankfully, talking about it energizes me! especially because it was something that I found super confusing in undergrad – and I want to show people it’s actually pretty rad!⠀The movie is new (09/17/21) but the text is adapted from 12/29/20

ATP’s kinda like arcade tokens. You go to an arcade and can stick in different forms of money and the machine will spit out tokens that you can use on any game. The different forms of money your cells start with are things like sugars, fats, and proteins, but they all eventually can give you ATP – and once you have the ATP there’s no “money trail” – the ATP all looks the same & can be “spent” anywhere – the “games” your cells plays have some pretty cool “prizes” – molecules like DNA, RNA, proteins, and lipids (fats). ⠀

You get ATP (and ADP, and AMP, and all sorts of stuff) from your food, but you don’t just build up an endless stock of it because ATP isn’t just used for energy. In fact, it’s one of the 4 RNA letters (nucleotides) and it can serve as a building block for other things or its atoms can be “recycled” to make things, so you don’t want to have a big cache of it that can get “looted.” (note: your muscles store some backup energy in the form of creatine phosphate, which can be used to quickly make ATP, and you can learn more about this reserve stock here: http://bit.ly/creatineatp  )⠀

To understand why ATP’s “high energy currency” you need to know a little about this molecule.  So, what is ATP on the molecular level? ATP stands for Adenosine Triphosphate. Adenosine’s an RNA letter – it has a ribose sugar hooked up to a “nitrogenous base” called adenine (A). That A can base-pair (form specific hydrogen bonds) with U or T, making it great for holding genetic info, but it’s the phosphate part that we care about when it comes to energy (although that A part helps the enzymes involved recognize it & use it so we do need it even here!)⠀

The phosphates are important because they’re basically really concentrated negative charges clamped together like a spring. Phosphate (PO₄³⁻) has a central phosphorous (P) atom connected to 4 oxygen (O) atoms. Like all atoms, these are made up of smaller “subatomic particles” – positively-charged protons and neutral neutrons, which hang out together in a dense central core called the atomic nucleus, and negatively-charged electrons which whizz around that nucleus in an “electron cloud.” Molecules form when atoms link up together by sharing pairs of electrons (we call such linkages covalent bonds). 

If the # of protons = # of neutrons, a molecule is neutral overall. But if there’s an imbalance, a molecule is charged (and we call it an ion). Phosphate has “extra” electrons (e⁻) so it’s ➖ charged. Like charges repel, so phosphates don’t like to be next to each other. Therefore, it takes effort (in the form of energy (E)) to bring & hold phosphates together (like compressing a spring) – so when they’re broken apart that E’s freed to be used for other things like paying cost of linking nucleotides together in the process of DNA polymerization. And if you can hold them together, you can store that “potential energy” like you store game-playing potential in an arcade token.

Bonds between the phosphates are considered “high energy” meaning they have high chemical potential energy. Energy is the ability to do work. And a common definition of work is basically “moving matter” – so just like an uncoiling spring can push away nearby things, the energy released when a phosphate-phosphate bond is broken can get used by nearby molecules to do things, like hold together other atoms that would rather be left alone (e.g. ATP can be “spent” to build molecules like DNA or proteins).

note: building processes are collectively referred to as “anabolism” and they’re the counterpart to “catabolism,” which refers to breaking-down processes. Together, anabolism and catabolism give you “metabolism” – and umbrella term for the biological making and breaking of molecules! 

Potential energy is easiest to see in terms of kinetic potential energy. Kinetic energy is energy of movement and if you think of a bowling ball at the top of a mountain or a roller coaster car about to drop down, potential energy is high at the top (lots of dropping potential) and low at the bottom (Earth’s crust is pretty hard to drop through). And energy has to be conserved, so energy had to get released and/or used up between the top and the bottom of the hill. ⠀

If you didn’t have the roller coaster tracks and you just had to hold up the car and keep it from dropping, that’d be really hard – you’d have to use a lot of energy to prevent it from spending that energy. And that car-holding-up is basically the job faced, on the molecular scale, by ATP. The energy investment is basically getting the Ps to stay together so you can “let go” in a controlled manner and use the released energy for specific purposes. And the “holder” is the bonds between the Ps. ⠀

The T in ATP is for Triphosphate (3 phosphates in a row) – but when you “let go” you go from ATP to ADP (if you let go of just the end phosphate (which we call the gamma (γ) phosphate) or AMP (adenosine MONOphosphate(AMP)) if you let go of the last 2 (γ AND β). In both cases you let go of some “free” phosphate(s) – When phosphates are on their own (free) we call them INORGANIC phosphate: orthophosphate when just 1 (Pi) & pyrophosphate when 2 (PPi) (inorganic because they’re not hooked up to any carbon-y thing).⠀

The more phosphates in a row, the more potential E, so ATP has more potential E than ADP, and there are 3 main types of E-money-transferers (i.e. molecules which transfer phosphate around)⠀

  • kinases transfer phosphates from ATP (or another NTP) (organic phosphate) to another molecule⠀
  • phosphorylases transfer phosphate from inorganic phosphates to another molecule ⠀

⚠️ Don’t confuse those with the 3rd type, phosphatases, which remove phosphate(s) from molecules (ie reversing what the kinases and phosphorylases did)⠀

And one last type of very important consumer of E-money is the ATPases, which simply pluck off the gamma phosphate (essentially transferring it to water) and use the energy fuel all sorts of important things like ion channels (trivia – one third of our massive ATP turn over every day is for one enzyme, a membrane protein that maintains ion gradients across cells).⠀

You see kinases a lot in metabolic pathways because they can make it easier to alter molecules at specific places. For instance, if you look at a sugar molecule you see a hydrocarbon skeleton with a bunch of -OH’s sticking off. How the heck is an enzyme (reaction-mediator) supposed to know where to break it or add something new, or whatever it is you want it to do? But what if you stuck a phosphate where you want to break it – voila! now you have an “over here!” sign. The phosphate group kinda “bribes” that enzyme with energy and makes a site vulnerable to change. 

Additionally, because the phosphorylation step spends energy, it can serve as a sort of “commitment step” to dissuade a reaction from happening in the opposite direction. For example, you see this in glycolysis (sugar-breakdown), where there are several “committed steps” which involve phosphorylation. Unlike the other steps in the glycolysis pathway which are easily reversible, these steps are so unfavorable in the “backwards” direction that they’re considered effectively irreversible (although there’s no such thing as a truly irreversible reaction). By regulating the phosphorylation (in part in response to how much energy is available) your cells can control how much sugar gets broken down when. The first glucose phosphorylation also plays the role of trapping glucose inside your cells because, once phosphorylated, it can’t sneak out! http://bit.ly/metabolismglycolysis 

Those examples were kinases phosphorylating metabolites, but some kinases are specialized for phosphorylating proteins, typically at the amino acids (protein letters) Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y) and, especially in bacteria, Histidine (His, H). Proteins are long chains of amino acids which fold up based on those amino acids’ unique chemical properties to get their beautiful 3-D shapes. If you add a phosphate group, it’s like adding a weird bulky item to your suitcase after you packed it and now you have to rearrange things. So phosphorylation can make proteins change their shape (undergo conformational change) which can activate or inactivate them. And phosphorylation can also create binding sites for other molecules which aren’t interested in the non-phosphorylated form but find the phosphorylated form oh-so-attractive… https://bit.ly/kinasesandphosphorylation

A while back I got a surprise gift in the mail – Dr. Alexandra Newton, president of the IUBMB, and I had been talking about how we had “crushes” on ATP – that’s pretty normal, right? Who cares! Anyways, she was telling me about this book she loves called “For the Love of Enzymes: The Odyssey of a Biochemist” by Arthur Kornberg (Nobel laureate who discovered DNA Polymerase (enzyme that links together DNA letters) and then one day it showed up in my mailbox! THANK YOU AGAIN! ⠀

It has some really cool stats on ATP. Here are just a few…⠀

  • intake of 2500 calories (which are actually kilocalories) corresponds to the turnover of ~180kg (400lb) of ATP⠀
  • your body only holds ~50g (~1/10 lb) of ATP at a time – so in order to reach that 180 it has to be constantly turning it over – so that ~50g gets turned over ~4,000 times PER DAY!!!!! ⠀
    • If we get all mole-y about it, the molecular weight of ATP is 517.18 g/mol. A mole is the biochemist’s “dozen” and it means ~6×10²³ of something.  So a little of that dimensional analysis I love …⠀http://bit.ly/dimensionalanalysising 
      • 50g x (1 mol/507.18 g) x (6×10²³ ATP molecules)/mol) = ~6 x 10²² ATP molecules⠀
      • …and you see that 50g of ATP is ~60 sextillion molecules of ATP (6×10²²) so, on average, the “last” phosphate (the gamma one) gets taken off & added back on 3 times per minute.⠀

so, in summary: break down food (catabolism) -> take the energy that was being used to hold the atoms of the food together (break molecular bonds) and store that energy in the universal cellular energy currency of ATP (use the energy from the food to add a phosphate to ADP to form ATP – this is like making a spring thicker while clamping it down harder – the negative charges of the phosphates repel each other so the bonds between the phosphates have “high chemical potential energy” – basically if you “let go” they’ll happily break off and release the energy that was being used to keep them clamped together⠀

when you need energy, “cash in” the ATP – you let it let go of that last phosphate (in a controlled manner so that, even though we call it “combustion” it’s not like fireworks go off in your cells)⠀

more on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0

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