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Deuterium and its impact on living organisms

Abstract

The rare stable isotope of hydrogen, deuterium, has fascinated researchers since its discovery in the 1930s. Subsequent large-scale production of deuterium oxide, commonly known as heavy water, became a starting point for further research. Deuterium exhibits unique physicochemical properties as well as having the strongest kinetic isotope effects among all other elements. Moreover, a broad variety of morphological and physiological changes have been observed in deuterium-treated cells and organisms, including changes in fundamental processes such as cell division or energy metabolism. Even though our understanding of such alterations is still insufficient, it is evident that some of them make growth in a deuterium-enriched environment a challenging task. There seems to be certain species-specific limits to their tolerance to heavy water, where some organisms are unable to grow in heavy water whilst others have no difficulties. Although the effects of deuterium on living organisms are, in general, negative, some of its applications are of great biotechnological potential, as is the case of stable isotope-labelled compounds or deuterated drugs.

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References

  • Acién Fernandez FG, Fernández Sevilla JM, Egorova-Zachernyuk TA, Molina Grima E (2005) Cost-effective production of 13C, 15N stable isotope-labelled biomass from phototrophic microalgae for various biotechnological applications. Biomol Eng 22:193–200

    PubMed  Google Scholar 

  • Amarose A, Czajka DM (1962) Cytopathic effects of deuterium oxide on the male gonads of the mouse and dog. Exp Cell Res 26:43–61

    CAS  PubMed  Google Scholar 

  • Apt KE, Behrens PW (1999) Commercial developments in microalgal biotechnology. J Phycol 35:215–226

    Google Scholar 

  • Araguas-Araguas L, Froehlich K, Rozanski K (2000) Deuterium and oxygen-18 isotope composition of precipitation and atmospheric moisture. Hydrol Process 14:1341–1355

    Google Scholar 

  • Berg T, Strand DH (2011) (1)(3) C labelled internal standards--a solution to minimize ion suppression effects in liquid chromatography-tandem mass spectrometry analyses of drugs in biological samples? J Chromatogr A 1218:9366–9374

    CAS  PubMed  Google Scholar 

  • Berry D et al (2014) Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. P Natl Acad Sci USA:E194–E203

    Google Scholar 

  • Bhosale P, Serban B, Bernstein PS (2006) Production of deuterated lutein by Chlorella protothecoides and its detection by mass spectrometric methods. Biotechnol Lett 28:1371–1375

    CAS  PubMed  Google Scholar 

  • Black A, Cole T (2000) Within-and between-subject variation in energy expenditure measured by the doubly-labelled water technique: implications for validating reported dietary energy intake. Eur J Clin Nutr 54:386–394

    CAS  PubMed  Google Scholar 

  • Blake MI, Crespi HL, Katz JJ (1975) Studies with deuterated drugs. J Pharm Sci 64:367–391

    CAS  PubMed  Google Scholar 

  • Braman V, Graham P, Cheng C, Turnquist D, Harnett M, Sabounjian L, Shipley J (2013) A randomized phase I evaluation of CTP-499, a novel deuterium-containing drug candidate for diabetic nephropathy. Clin Pharm Drug Dev 2:53–66

    CAS  Google Scholar 

  • Cardoso MV, Carvalho LV, Sabadini E (2012) Solubility of carbohydrates in heavy water. Carbohydr Res 353:57–61

    CAS  PubMed  Google Scholar 

  • Cioni P, Strambini GB (2002) Effect of heavy water on protein flexibility. Biophys J 82:3246–3253

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cong F, Zhang Y, Sheng H, Ao Z, Zhang S, Wang J (2010) Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis. Exp Ther Med 1:277–283

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crespi H, Katz J (1966) Fluorescence studies on deuterated Chlorella vulgaris. Biochim Biophys Acta 120:19–22

    PubMed  Google Scholar 

  • Crespi HL, Conrad SM, Uphaus RA, Katz JJ (1960) Cultivation of microorganisms in heavy water. Ann N Y Acad Sci 84:648–666

    CAS  PubMed  Google Scholar 

  • Czajka DM, Finkel AJ (1960) Effect of deuterium oxide on the reproductive potential of mice. Ann N Y Acad Sci 84:770–779

    CAS  PubMed  Google Scholar 

  • Czajka DM, Finkel AJ, Fischer CS, Katz JJ (1961) Physiological effects of deuterium on dogs. Am J Phys-Legacy Content 201:357–362

    Google Scholar 

  • de Kouchkovsky Y, Haraux F, Sigalat C (1982) Effect of hydrogen-deuterium exchange on energy-coupled processes in thylakoids. FEBS Lett 139:245–249

    Google Scholar 

  • Dowse HB, Palmer JD (1972) The chronomutagenic effect of deuterium oxide on the period and entrainment of a biological rhythm. Biol Bull 143:513–524

    CAS  PubMed  Google Scholar 

  • Fuks B, Homblé F (1996) Mechanism of proton permeation through chloroplast lipid membranes. Plant Physiol 112:759–766

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gant TG (2013) Using deuterium in drug discovery: leaving the label in the drug. J Med Chem 57:3595–3611

    PubMed  Google Scholar 

  • Gireesh T, Jayadeep A, Rajasekharan KN, Menon VP, Vairamany M, Tang G, Nair PP, Sudhakaran PR (2001) Production of deuterated β-carotene by metabolic labelling of Spirulina platensis. Biotechnol Lett 23:447–449

    CAS  Google Scholar 

  • Gouw JW, Tops BB, Krijgsveld J (2011) Metabolic labeling of model organisms using heavy nitrogen (15N). Method Mol Biol 753:29–42

    CAS  Google Scholar 

  • Gregg CT, Hutson JY, Prine JR, Ott DG, Furchner JE (1973) Substantial replacement of mammalian body carbon with carbon-13. Life Sci 13:775–782

    CAS  PubMed  Google Scholar 

  • Gross PR, Spindel W (1960) Mitotic arrest by deuterium oxide. Science 131:37–39

    CAS  PubMed  Google Scholar 

  • Gyongyi Z, Somlyai G (2000) Deuterium depletion can decrease the expression of c-myc, Ha-ras and p53 gene in carcinogen-treated mice. In Vivo 14:437–440

    CAS  PubMed  Google Scholar 

  • Haon S, Auge S, Tropis M, Milon AJ (1993) Low cost production of perdeuterated biomass using methylotrophic yeasts. Labelled Compd Radiopharm 22:1053–1063

    Google Scholar 

  • Harbeson SL, Morgan AJ, Liu JF, Aslanian AM, Nguyen S, Bridson GW, Brummel CL, Wu L, Tung RD, Pilja L, Braman V, Uttamsingh V (2017) Altering metabolic profiles of drugs by precision deuteration 2: discovery of a deuterated analog of ivacaftor with differentiated pharmacokinetics for clinical development. J Pharmacol Exp Ther 362:359–367

    CAS  PubMed  Google Scholar 

  • Hill R, Davies P (2001) The validity of self-reported energy intake as determined using the doubly labelled water technique. Br J Nutr 85:415–430

    CAS  PubMed  Google Scholar 

  • Hirai K, Tomida M, Kikuchi Y, Ueda O, Ando H, Asanuma N (2010) Effects of deuterium oxide on Streptococcus mutans and Pseudomonas aeruginosa. The Bulletin of Tokyo Dental College 51:175–183

    CAS  PubMed  Google Scholar 

  • Hirakura Y, Sugiyama T, Takeda M, Ikeda M, Yoshioka T (2011) Deuteration as a tool in investigating the role of protons in cell signaling. Biochim Biophys Acta 1810:218–225

    CAS  PubMed  Google Scholar 

  • Hughes AM, Bennett EL, Calvin M (1959) Production of sterility in mice by deuterium oxide. P Nat Acad Sci USA 45:581–586

    CAS  Google Scholar 

  • Hughes AM, Bennett EL, Calvin M (1960) Further studies on sterility produced in male mice by deuterium oxide. Ann N Y Acad Sci 84:763–769

    CAS  PubMed  Google Scholar 

  • Chakrabarti G, Kim S, Gupta MLJ, Barton JS, Himes RH (1999) Stabilization of tubulin by deuterium oxide. Biochemistry 38:3067–3072

    CAS  PubMed  Google Scholar 

  • Chorney W, Scully NJ, Crespi HL, Katz JJ (1960) The growth of algae in deuterium oxide. Biochim Biophys Acta 37:280–287

    CAS  PubMed  Google Scholar 

  • Itoh TJ, Sato H (1984) The effects of deuterium oxide (2H2O) on the polymerization of tubulin in vitro. Biochim Biophys Acta 800:21–27

    CAS  PubMed  Google Scholar 

  • Jacques V, Czarnik AW, Judge TM, Van der Ploeg LH, DeWitt SH (2015) Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs. P Natl Acad Sci USA:201417832

  • Katz JJ (1960) Chemical and biological studies with deuterium. Am Sci 48:544–580

    CAS  Google Scholar 

  • Katz JJ, Crespi HL (1966) Deuterated organisms: cultivation and uses. Science 151:1187–1194

    CAS  PubMed  Google Scholar 

  • Khaled MA, Lukaski HC, Watkins CL (1987) Determination of total body water by deuterium NMR. Am J Clin Nutr 45:1–6

    CAS  PubMed  Google Scholar 

  • Knapp DR, Gaffney TE (1972) Use of stable isotopes in pharmacology-clinical pharmacology. Clin Pharmacol Ther 13:307–316

    CAS  PubMed  Google Scholar 

  • Kopf SH, Sessions AL, Cowley ES, Reyes C, van Sambeek L, Hu Y, Orphan VJ, Kato R, Newman DK (2016) Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum. P Natl Acad Sci USA 113:E110–E116

    CAS  Google Scholar 

  • Kotyk A, Dvořáková M, Koryta J (1990) Deuterons cannot replace protons in active transport processes in yeast. FEBS Lett 264:203–205

    CAS  PubMed  Google Scholar 

  • Kushner DJ, Baker A, Dunstall TG (1997) Biotechnological potential of heavy water and deuterated compounds. In: Levin M, Grim C, Angle JS (eds) Proceedings of Biotechnology Risk Assessment Symposium, Ottawa, Canada, June 23–25, 1996. University of Maryland Biotechnology Institute Publication, pp 75–89

  • Laissue J, Stoner R (1979) Deuterium isotope effects on lymphoid tissues and humoral antibody responses in mice. Virchows Arch 383:149–166

    CAS  Google Scholar 

  • Lamprecht J, Schroeter D, Paweletz N (1991) Derangement of microtubule arrays in interphase and mitotic PtK2 cells treated with deuterium oxide (heavy water). J Cell Sci 98:463–473

    PubMed  Google Scholar 

  • Lane AN, Fan TW (2015) Regulation of mammalian nucleotide metabolism and biosynthesis. Nucleic Acids Res 43:2466–2485

    CAS  PubMed  PubMed Central  Google Scholar 

  • Laskay G, Somlyai G, Jancsó G (2001) Reduced deuterium concentration of water stimulates O 2-uptake and electrogenic H+-efflux in the aquatic macrophyte Elodea canadensis. Jpn J Deuterium Sci 10:17–23

    CAS  Google Scholar 

  • Lehmann WD (2016) A timeline of stable isotopes and mass spectrometry in the life sciences. Mass Spectrom Rev

  • Lewis GN (1933) The biochemistry of water containing hydrogen isotope. J Am Chem Soc 55:3503–3504

    CAS  Google Scholar 

  • Lewis GN (1934) The biology of heavy water. Science 79:151–153

    CAS  PubMed  Google Scholar 

  • Lewis GN, Cornish RE (1933) Separation of the isotopic forms of water by fractional distillation. J Am Chem Soc 55:2616–2617

    CAS  Google Scholar 

  • MacDonald A, Reed R (1956) The determination of deuterium by the mass-spectrometric method. Analyst 81:401–403

    CAS  Google Scholar 

  • Manson LA, Defendi V, Hartzell RW Jr, Kritchevsky D (1960) Effect of deuterium oxide on growth of HeLa, L and L-5178Y cells. P Soc Exp Biol Med 105:481–483

    CAS  Google Scholar 

  • Marsland D, Hecht R (1968) Cell division: combined anti-mitotic effects of colchicine and heavy water on first cleavage in the eggs of Arbacia punctulata. Exp Cell Res 51:602–608

    CAS  PubMed  Google Scholar 

  • Mohan VS, Crespi HL, Katz JJ (1962) Nutritional requirements for the cultivation of fully deuterated yeasts Torulopsis utilis and Saccharomyces cerevisiae. Nature 193:189–190

    CAS  Google Scholar 

  • Mosin O, Ignatov I, Skladnev D, Shvets V (2014) Studying of phenomenon of biological adaptation to heavy water. Eur J Mol Biotechnol 6:180–209

    CAS  Google Scholar 

  • Mueller D, Heinzle E (2013) Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures. Curr Opin Biotechnol 24:54–59

    CAS  PubMed  Google Scholar 

  • Neubauer C, Sessions A, Booth I, Bowen B, Kopf S, Newman D, Dalleska N (2018) Towards measuring growth rates of pathogens during infections by D2O-labeling lipidomics. Rapid Commun Mass Sp 32:2129–2140

    CAS  Google Scholar 

  • Olgun A (2007) Biological effects of deuteronation: ATP synthase as an example. Theor Biol Med Model 4:9

    PubMed  PubMed Central  Google Scholar 

  • Panda D, Chakrabarti G, Hudson J, Pigg K, Miller HP, Wilson L, Himes RH (2000) Suppression of microtubule dynamic instability and treadmilling by deuterium oxide. Biochemistry 39:5075–5081

    CAS  PubMed  Google Scholar 

  • Raghavan CV, Super DM, Chatburn RL, Savin SM, Fanaroff AA, Kalhan SC (1998) Estimation of total body water in very-low-birth-weight infants by using anthropometry with and without bioelectrical impedance and H2 [(18) O]. Am J Clin Nutr 68:668–674

    CAS  PubMed  Google Scholar 

  • Saha SK, Hayes J, Moane S, Murray P (2013) Tagging of biomolecules with deuterated water (D2O) in commercially important microalgae. Biotechnol Lett 35:1067–1072

    CAS  PubMed  Google Scholar 

  • Salomonsson L, Branden G, Brzezinski P (2008) Deuterium isotope effect of proton pumping in cytochrome c oxidase. Biochim Biophys Acta 1777:343–350

    CAS  PubMed  Google Scholar 

  • Sen A, Balamurugan V, Rajak KK, Chakravarti S, Bhanuprakash V, Singh RK (2009) Role of heavy water in biological sciences with an emphasis on thermostabilization of vaccines. Expert Rev Vaccines 8:1587–1602

    CAS  PubMed  Google Scholar 

  • Schwarcz HP, Schoeninger MJ (1991) Stable isotope analyses in human nutritional ecology. Am J Phys Anthropol 34:283–321

    Google Scholar 

  • Somlyai G, Jancsó G, Jákli G, Vass K, Barna B, Lakics V, Gaál T (1993) Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS Lett 317:1–4

    CAS  PubMed  Google Scholar 

  • Steinberg D, Mize CE, Avigan J, Fales HM, Eldjarn L, Try K, Stokke O, Refsum S (1967) Studies on the metabolic error in Refsum’s disease. J Clin Invest 46:313–322

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi TC, Sato H (1982) Thermodynamic analysis of the effect of D2O on mitotic spindles in developing sea urchin eggs. Cell Struct Funct 7:349–357

    CAS  Google Scholar 

  • Takeda H, Nio Y, Omori H, Uegaki K, Hirahara N, Sasaki S, Tamura K, Ohtani H (1998) Mechanisms of cytotoxic effects of heavy water (deuterium oxide: D2O) on cancer cells. Anti-Cancer Drugs 9:715–725

    CAS  PubMed  Google Scholar 

  • Uemura T, Moritake K, Akiyama Y, Kimura Y, Shingu T, Yamasaki T (2002) Experimental validation of deuterium oxide—mediated antitumoral activity as it relates to apoptosis in murine malignant astrocytoma cells. J Neurosurg 96:900–908

    CAS  PubMed  Google Scholar 

  • Unno K, Hagima N, Kishido T, Okada S, Oku N (2005) Deuterium-resistant algal cell line for D labeling of heterotrophs expresses enhanced level of Hsp60 in D2O medium. Appl Environ Microbiol 71:2256–2259

    CAS  PubMed  PubMed Central  Google Scholar 

  • Urey HC (1933) The separation and properties of the isotopes of hydrogen. Science 78:566–571

    CAS  PubMed  Google Scholar 

  • Urey HC, Brickwedde FG, Murphy GM (1932) A hydrogen isotope of mass 2. Phys Rev 39:164–165

    CAS  Google Scholar 

  • Uttamsingh V, Gallegos R, Liu JF, Harbeson SL, Bridson GW, Cheng C, Wells DS, Graham PB, Zelle R, Tung R (2015) Altering metabolic profiles of drugs by precision deuteration: reducing mechanism-based inhibition of CYP2D6 by paroxetine. J Pharmacol Exp Ther 354:43–54

    CAS  PubMed  Google Scholar 

  • Vasilescu V, Katona E (1986) Deuteration as a tool in investigating the role of water in the structure and function of excitable membranes. Methods Enzymol 127:662–678

    CAS  PubMed  Google Scholar 

  • Walker DK, Thaden JJ, Deutz NE (2015) Application of gas chromatography–tandem mass spectrometry (GC/MS/MS) for the analysis of deuterium enrichment of water. J Mass Spectrom 50:838–843

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Huang WE, Cui L, Wagner M (2016) Single cell stable isotope probing in microbiology using Raman microspectroscopy. Curr Opin Biotechnol 41:34–42

    CAS  PubMed  Google Scholar 

  • Washburn EW, Smith ER (1933) The isotopic fractionation of water by distillation and by adsorption. Journ Chem Phys 1:426–426

    CAS  Google Scholar 

  • Webhofer C, Zhang Y, Brusis J, Reckow S, Landgraf R, Maccarrone G, Turck CW, Filiou MD (2013) (1)(5) N metabolic labeling: evidence for a stable isotope effect on plasma protein levels and peptide chromatographic retention times. J Proteome 88:27–33

    CAS  Google Scholar 

  • West JB, Bowen GJ, Cerling TE, Ehleringer JR (2006) Stable isotopes as one of nature’s ecological recorders. Trends Ecol Evol 21:408–414

    PubMed  Google Scholar 

  • Wu R, Georgescu M-M, Delpeyroux F, Guillot S, Balanant J, Simpson K, Crainic R (1995) Thermostabilization of live virus vaccines by heavy water (D2O). Vaccine 13:1058–1063

    CAS  PubMed  Google Scholar 

  • Yang J (2016) Deuterium. In: Deuterium: discovery and applications in organic chemistry. Elsevier, Amsterdam

    Google Scholar 

  • Zachleder V, Vítová M, Hlavová M, Moudříková Š, Mojzeš P, Heumann H, Becher JR, Bišová K (2018) Stable isotope compounds - production, detection, and application. Biotechnol Adv 36:784–797

    CAS  PubMed  Google Scholar 

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Acknowledgements

The work was supported by the Grant Agency of the Czech Republic (grant no. 17-06264S) and by the National Programme of Sustainability I (project no. LO1416).

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Correspondence to Kateřina Bišová.

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Dedicated to the memory of Dr. Ivan Šetlík.

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Kselíková, V., Vítová, M. & Bišová, K. Deuterium and its impact on living organisms. Folia Microbiol 64, 673–681 (2019). https://doi.org/10.1007/s12223-019-00740-0

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