The role of deuterium in molecular evolution by Oleg V Mosin

A pretty interesting article that Koch sent to me a while ago. It has been backlogged for some time and I’m finally able to read it now. The English is a bit rough for me to understand but I’ll summarize what I figured out here. The important thing is that there are tons of references. So anything I don’t understand here I can look back at the original papers and clear up any misunderstandings.

Mosin starts with a nice introduction to the physical history of deuterium, and speaks of something that I only just recently learned: that all the deuterium in the universe was created in the beginning of the universe! Stars use it faster than they make it, so while there is some recycling, eventually this resource will be depleted.

He then talks about the chemical nature of deuterium in molecular biology. I’m not 100% on this but I think he points out some studies that show that introduction of deuterium to amino acids and proteins disrupts the nature of the folding of these molecules.

I’ve mentioned several times that H-D exchange is a real phenomenon (and one that I don’t understand the extent of). When deuterium is introduced to a folded protein (for instance) there is some exchange with the exterior hydrogens (which Mosin calls exchangable molecules) which effects the hydrogen interactions between the molecule and the surrounding environment (water) and also some self bonding of the molecule itself. As I’ve learned hydrogen bonding, while a weak interaction, is crucial to a lot of fundamental processes of life.

Not only this, but deuterium introduction also affects folding when these macromolecules are made from scratch (de novo as Mosin states). The reasoning is that D-exchange occurs easily at the fundamental level (he states something about hydrophobic interactions on the macromolecule level preventing deuterium from penetrating inside the molecule) and this can change the very structure that is supposed to form in the presence of regular hydrogen.

Mosin then goes on to discuss cell division being affected by heavy water. Here he uses a bunch of jargon that I’m not familiar with (I have almost no understanding of the inner workings of cell division).

Next he starts discussing a topic that Steve and I (and Bill Hooker has brought up from time to time) have discussed. He mentions that strains of e. coli have been shown to be resistant to heavy water. He talks of some mutagenic properties, but I’m not caught up on this aspect yet. But I will mention that I have interest in these studies because I want to perform some experiments that demonstrate the effect of water on D2O resistant organisms. Suppose I grow e. coli in 99% D2O. Is H2O as toxic to this organism as D2O is to H2O adapted life? Consider this my first official proclamation of this new study!

He also makes an interesting comment:

Secondly, if the structure of fully deuterated proteins may be stabilized in heavy water in a view of duarability of deuterated bonds, it would be very interesting to study the thermo-stability of [U -2H]labeled proteins for using them directly in processes going at high temperatures.

Another of my project interests is to investigate the stability of proteins (particularly kinesin) in heavy water. What Mosin mentions here is an offshoot of organism resistance to heavy water. Supposing we get fully adapted molecules (adapted to D2O meaning there are mostly D’s where there would normally be H’s), it would be interesting to study the stability of these proteins. This is something that I hadn’t thought of. To me this can be restated as: Are deuterated proteins in heavy water more, less, or as stable as traditional proteins in light water (H2O)?

The implications of that question are staggering. If we have a mechanism to generate deuterated proteins via heavy water adapted cells (cloning in D2O with deuterated cells gets my senses tingling!) and can demonstrate a greater thermo-stability, increased protein lifespan, etc that would be quite remarkable! Imagine the potential for bio devices that can be made and stored at room temperature without the fear of protein degradation!

Back on track, I realize now that Mosin et al may be experts with regard to D2O cloning as he has a couple papers from 1996 (that he references) that talks about the adaptation to heavy water. I’ll have to check those out.

At this point the language barrier and the technical jargon are too much for me to overcome. I’m probably like 2/3 done, and I no longer understand what Mosin is talking about. But a few things are clear:

  1. Heavy water’s role in life is more profound than anyone could have ever guessed. There are so many intricacies that heavy water could affect, it’s a wonder that my seeds can even grow in 33% D2O!
  2. Adapting life to grow in heavy water is possible! Maybe even easy to do? While it may not be worth the time trying to learn to grow stuff in heavy water, it seems there may be some commercial solutions. Let the investigation begin.
  3. It seems very clear to me that removing all D2O from normal (hydrogen based) organism should have some sort of effect. I just have to figure out how to witness this effect. I think using simpler organisms (not as evolved?) should yield better results. Mosin mentions that is is easier to get life to adapt to D2O if the organism isn’t as evolved: “For example, there are halophilic bacteria that are being the most primitive in the evolutionary plan, and therefore, they practically not requiring to carry out a special adaptation methods to grow on heavy water. On the contrary, bacills (eubacteria) and methylotrophs (gram-negative bacteria) worse adapted to heavy water . (sic)” (Now you see why I am giving up for now!)
  4. It seems reasonable to consider (and likely) that regular water would be toxic to deuterium adjusted life just as heavy water is toxic to hydrogen based life.

In case you decided not to read the linked article and have read these ramblings here is the list of references that I will sort through this upcoming week:

  • Campbell I. D., and Dwek. Biological Spectroscopy. Benjamin/Cummings, Menlo Park, Calif. 1990.
  • Covington A. K., Robinson R. A., and Bates R. G. // J. Phys. Chem. 1966. V. 70. P. 3820.
  • Еgorova T. A., Mosin O. V., Shvets V. I., et al. // Biotechnologija. 1993. N.8. P. 21-25.
  • Fesic S. W. and Zuiderweg E. R. // Quarterly Reviews of Biophysics. – 1990. – V.23. – N.2. – P. 97-131.
  • Johnson W. C. Protein secondary structure and circular dichroism: A practical guide. Proteins Struct. Funct. Genet. 1990. 7:205-214.
  • Glasoe P. K., and Long F. A. // J. Phys. Chem. 1960. V. 64. P. 188.
  • Hogan C. J. // Scientific American. December 1996. P. 36-41.
  • Karnaukhova E. N., Mosin O. V., and Reshetova O. S. // Amino Acids. 1993. V.5. ¹.1.P.125.
  • Katz J., Crespy H. L. // Pure Appl. Chem. 1972. V. 32. P. 221-250.
  • Lewis G. N. // Science. 1934. V. 79. P. 151. (We should all recognize this one!)
  • Mathews C. K., van Holde K. E. Biochemistry Benjamin/Cummings, Menlo Park, Calif. 1996. P. 204-210.
  • Mosin O. V., Karnaukhova E. N., Skladnev D. A., et al. // Biotechnologija. 1993. ¹.9. P. 16-20.
  • Mosin O. V., Karnaukhova E. N., Pshenichnikova A. B., Reshetova O. S. Electron impact spectrometry in bioanalysis of stable isotope labeled bacteriorhodopsin. in: Sixth International Conference on Retinal Proteins. 19-24 June 1994. Leiden. The Netherlands. P.115.
  • Mosin O. V., Karnaukhova E. N., and Skladnev D. A. Preparation of 2H-and 13C-amino acids via bioconvertion of C1-substrates. in: 8th International Symposium on Microbial Growth on C1 Compounds. 27 August-1 September 1995. San Diego. U.S.A. P. 80.
  • Mosin O. V., Skladnev D. A., Egorova T. A., Yurkevich A. M., Shvets V. I. // Biotechnologija. ¹3. 1996a. P. 3-12.
  • Mosin O. V., Egorova T. A., Chebotaev . B., Skladnev D. A., Yurkevich A. M., Shvets V. I. // Biotechnologija. 1996b. N 4. P. 27-34.
  • Mosin O. V., Kazarinova L. A., Preobrazenskaya K. A., Skladnev D. A., Yurkevich A. M.,
  • Shvets V. I. // Biotechnologija. 1996c. N 4. P. 19-26.
  • Mosin O. B., Skladnev D. A., Egorova T. A., Shvets V. I // Bioorganicheskaja khimia. 1996d. V. 22. N 10-11. P. 861-874.
  • Skladnev D. A., Mosin O. V., Egorova T. A., Eremin S. V., Shvets V. I. Methylotrophic bacteria as sourses of 2H-and 13C-amino acids. // Biotechnologija. N 5. 1996. P. 14-22.
  • Shvets V. I., Yurkevich A. M., Mosin O. V., Skladnev D. A // Karadeniz Journal of Medical Sciences. 1995. V.8. N 4. P.231-232.
  • Thomson J. F. Biological Effects of Deuterium. 1963. Pergamon, New York.
    Tomita K., Rich A., de Loze C., and Blout E. R. // J. Mol. Biol. 1962. V. 4. P. 83.
    Wiberg K. B. // Chem. Rev. 1955. V. 55. P. 713.