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Why is it that when you denature protein that's it?

  1. Jul 9, 2010 #1
    Hello everyone,

    Why is that when denature protein you can't get it back to orginal shape. Practically it is obvious that when you burn something it is not going to come back for original shape but what is the chemical basis behind this. Are molecules loss or, heat loss or why is it this so. Why does extreme cooling can not get it back to orginal shape. Thanks :smile:
     
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  3. Jul 9, 2010 #2

    Andy Resnick

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    I'm not sure denaturing a protein is *always* irreversible. IIRC, it can be done reversibly, sometimes, for some proteins.

    http://pubs.acs.org/doi/abs/10.1021/ja01074a014

    But usually, the process of denaturing a protein is irreversible. The best I can figure out is the transition from the folded state to the unfolded state is associated with a decrease in the free energy

    www.jbc.org/content/258/13/7960.full.pdf

    Which means the entropy increased. That doesn't exactly explain *why* it's irreversible (since proteins get correctly folded all the time), but it's the best reason I can come up with. It seems to be an active area of research.
     
  4. Jul 9, 2010 #3

    Ygggdrasil

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    When refolding, many proteins can fall into a conformation that is a local free energy minimum but not the global free energy minimum (the native state). Often, the energy required to escape this free energy minimum is much larger than the thermal energy available from the environment. Therefore, escape from these misfolded states is extremely slow and we say that the protein is stuck in a kinetic trap. Cooling only makes this problem worse as it decreases the thermal energy, keeping misfolded proteins from having enough energy available to unfold and try to refold into the native state. How proteins avoid these kinetic traps in nature is still not well understood but may have something to do with the fact protein folding is coupled to translation and the presence of chaperon proteins inside cells that aid the folding process.

    Another pathway for misfolding is aggregation. Unfolding exposes the hydrophobic core of proteins. When two unfolded proteins collide, their hydrophobic cores can interact and bind them together through the hydrophobic effect. This is often problematic because the aggregated state may have a lower free energy than the folded state. Inside cells, chaperon proteins bind unfolded proteins to help prevent aggregation from occurring.
     
  5. Jul 10, 2010 #4
    so is this why an egg solidifies when you cook it ?
     
  6. Jul 10, 2010 #5

    Ygggdrasil

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    Probably, although I'm not too sure on the details.
     
  7. Jul 10, 2010 #6

    Andy Resnick

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  8. Jul 13, 2010 #7

    Lok

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    All reactions and transformations are reversible... in theory. It is just that some are so delicate that the conditions needed for the reverse transfomation are very improbable.

    E.g. Something like A+B=C+a photon. For the reverse to happen the photon needs to be of the same energy and it needs to hit C in an rather exact geometric direction for A and B to split back. Usually very unlikely.

    In protein denaturation there are several changes that happen in it's shape, so it is rather clear why the reverse reaction has very little chance and very demanding conditions.
     
  9. Jul 13, 2010 #8

    Pythagorean

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    seriously?
     
  10. Jul 13, 2010 #9

    Lok

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    Yes. Don't ignore the very slim chance paragraph, as it is at the core of what I'm saying.
     
  11. Jul 13, 2010 #10

    Pythagorean

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    I understand you're distinguishing between theory and practice. I thought entropy somehow damned some interactions to irreversibility, even in principle (theory).
     
  12. Jul 13, 2010 #11

    Lok

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    Never said anything about no exterior help to attain the necessary conditions, but thanks for pointing out the multitude of interpretations of my post.
     
  13. Jul 13, 2010 #12

    Pythagorean

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    It seems entropy actually isn't the culprit:

    (emphasis added)

    Then again, it seems entropy may be the culprit in the second definition (as 'reversibility' is dependent on the surroundings stability too, so external help wouldn't seem to help the matter).

    But I guess what's important is your definition of a reversible process. What is it:?
     
  14. Jul 13, 2010 #13

    Lok

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    I thought we are talking about chemical reactions and transformations. But go on..
     
  15. Jul 13, 2010 #14

    Ygggdrasil

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    One of the principles upon which chemistry is built is the principle of microscopic reversibility (http://en.wikipedia.org/wiki/Microscopic_reversibility). While reversible transformation may be difficult to achieve in practice, in many cases we can study reasonable approximations in the lab. If you look at the individual molecules in such a reaction, you can see that these molecules will sometimes spontaneously jump to a state of higher free energy. This does not contradict the second law of thermodynamics because themodynamics concerns itself with the behavior of large populations (ensembles) and not single molecules. We can reconcile the difference between the single molecule measurements and the ensemble by noting that transitions to the higher free energy state occur more rarely than transitions to the lower free energy state (or equivalently the lifetime of the higher free energy state is shorter than the lifetime of the lower free energy state). Thus, when you consider the population as a whole, you will see it move toward the lower free energy state even though individual molecules are transiting between the two states. This type of experiments demonstrates why we refer to chemical equilibrium as a dynamic process.

    In fact, such experiments have been done to study the folding of biological molecules such as proteins and nucleic acids. For example see this paper from Carlos Bustamante's and Susan Marqusee's labs: Cecconi et al. 2005 Direct Observation of the Three-State Folding of a Single Protein Molecule. Science 23: 2057 - 2060. doi:10.1126/science.1116702.
     
    Last edited: Jul 13, 2010
  16. Jul 13, 2010 #15

    alxm

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    Who said this? This is simply not true. For instance, pH denaturation usually is reversible.
     
  17. Jul 13, 2010 #16

    Pythagorean

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    I am. Chemical reactions aren't somehow void of thermodynamics that I know of. But you still haven't provided a definition, so we could be arguing tangent to each other.
     
  18. Jul 13, 2010 #17
    AFAIK, if black holes really do destroy information, the only way to irreversibly destroy something (change, etc) would be to drop it into a gravitational singularity. In practice, this is a pretty meaningless distinction, but in theory that is the only absolute barrier to reversibility that I'm aware of.
     
  19. Jul 13, 2010 #18

    Ygggdrasil

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    Some definitions that may potentially clear things up. The word "reversibility" in thermodynamics has a specific meaning that is very different from the non-scientific meaning for reversibility.

    Thermodynamic reversibility: A reversible transformation is one done slowly enough such that the system and surrounding are always at equilibrium. Under such conditions, the entropy of the universe stays the same (ΔSsurr + ΔSsys = 0).

    Thermodynamic irreversibility: An irreversible transformation is one in which the system and surroundings are not at equilibrium. In this case, the entropy of the universe increases (ΔSsurr + ΔSsys > 0). This makes the transformation irreversible because the entropy of the universe has irrevocably increased. Due to the second law of thermodynamics, you can never lower the entropy of the universe to the level it was at before the transformation occurred.

    Examples: Ice melting into water at 0oC is a thermodynamically reversible process (the ice and water are at equilibrium at 0oC). Ice melting into water at 25oC (or for that matter, any temperature above 0oC) is thermodynamically irreversible.

    Of course, both these examples of ice melting would be considered reversible in layperson's terms. All one would have to do to get back to the original state would be to cool the system back down.

    Because we're simply talking about proteins returning to their original shape after denaturation (not worrying about the total entropy change of the universe that occurred during this process), the layperson's definition is most relevant to the discussion.

    Lok's point that all reactions are reversible (in the layperson's sense) is generally true. In a chemical reaction, if there is a pathway from reactants to products, then products can be turned into reactants by the exact reverse of that pathway. Traversing the pathway in reverse may be extremely slow or very thermodynamically unfavorable, but it is theoretically possible. This statement, however, is probably not true in the sense of thermodynamic reversibility.

    The statement quoted by Pythagorean, which says that "perfectly reversible processes are impossible," refers to reversiblility only in the thermodynamic meaning.
     
    Last edited: Jul 13, 2010
  20. Jul 14, 2010 #19

    Lok

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    We are talking about to different things. Yet still even thermodynamics does not say reversability is impossible even in macro systems, just that it is more probable for pigs to fly on butterfly wings, while drunk.
     
  21. Jul 14, 2010 #20
    Ever see a drunken pig?... it's hilarious. A friend had a potbelly as a pet and it got into some rotten (read: fermented) apples. Hilarity ensued for all involved and I do believe that was the happiest pig I've ever seen. Bears, horses, and especially monkeys do much the same. In fact, some monkeys make their own "pruno" (http://www.drunkard.com/issues/01-05/0105-beer monkeys.htm), and vervet monkeys steal drinks from beachgoers. Is this a tangent? Hell yes. Was it worth it? You decide, but youtube has some priceless footage of bears drunk on fermented apples, vervets on the sauce, and other mammals with a predilection for ethanol that we share.

    Perhaps in the pig's mind it is flying on butterfly wings at this time? :wink:
     
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