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.
Similar content being viewed by others
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
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
Apt KE, Behrens PW (1999) Commercial developments in microalgal biotechnology. J Phycol 35:215–226
Araguas-Araguas L, Froehlich K, Rozanski K (2000) Deuterium and oxygen-18 isotope composition of precipitation and atmospheric moisture. Hydrol Process 14:1341–1355
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
Berry D et al (2014) Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. P Natl Acad Sci USA:E194–E203
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
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
Blake MI, Crespi HL, Katz JJ (1975) Studies with deuterated drugs. J Pharm Sci 64:367–391
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
Cardoso MV, Carvalho LV, Sabadini E (2012) Solubility of carbohydrates in heavy water. Carbohydr Res 353:57–61
Cioni P, Strambini GB (2002) Effect of heavy water on protein flexibility. Biophys J 82:3246–3253
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
Crespi H, Katz J (1966) Fluorescence studies on deuterated Chlorella vulgaris. Biochim Biophys Acta 120:19–22
Crespi HL, Conrad SM, Uphaus RA, Katz JJ (1960) Cultivation of microorganisms in heavy water. Ann N Y Acad Sci 84:648–666
Czajka DM, Finkel AJ (1960) Effect of deuterium oxide on the reproductive potential of mice. Ann N Y Acad Sci 84:770–779
Czajka DM, Finkel AJ, Fischer CS, Katz JJ (1961) Physiological effects of deuterium on dogs. Am J Phys-Legacy Content 201:357–362
de Kouchkovsky Y, Haraux F, Sigalat C (1982) Effect of hydrogen-deuterium exchange on energy-coupled processes in thylakoids. FEBS Lett 139:245–249
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
Fuks B, Homblé F (1996) Mechanism of proton permeation through chloroplast lipid membranes. Plant Physiol 112:759–766
Gant TG (2013) Using deuterium in drug discovery: leaving the label in the drug. J Med Chem 57:3595–3611
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
Gouw JW, Tops BB, Krijgsveld J (2011) Metabolic labeling of model organisms using heavy nitrogen (15N). Method Mol Biol 753:29–42
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
Gross PR, Spindel W (1960) Mitotic arrest by deuterium oxide. Science 131:37–39
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
Haon S, Auge S, Tropis M, Milon AJ (1993) Low cost production of perdeuterated biomass using methylotrophic yeasts. Labelled Compd Radiopharm 22:1053–1063
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
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
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
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
Hughes AM, Bennett EL, Calvin M (1959) Production of sterility in mice by deuterium oxide. P Nat Acad Sci USA 45:581–586
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
Chakrabarti G, Kim S, Gupta MLJ, Barton JS, Himes RH (1999) Stabilization of tubulin by deuterium oxide. Biochemistry 38:3067–3072
Chorney W, Scully NJ, Crespi HL, Katz JJ (1960) The growth of algae in deuterium oxide. Biochim Biophys Acta 37:280–287
Itoh TJ, Sato H (1984) The effects of deuterium oxide (2H2O) on the polymerization of tubulin in vitro. Biochim Biophys Acta 800:21–27
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
Katz JJ, Crespi HL (1966) Deuterated organisms: cultivation and uses. Science 151:1187–1194
Khaled MA, Lukaski HC, Watkins CL (1987) Determination of total body water by deuterium NMR. Am J Clin Nutr 45:1–6
Knapp DR, Gaffney TE (1972) Use of stable isotopes in pharmacology-clinical pharmacology. Clin Pharmacol Ther 13:307–316
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
Kotyk A, Dvořáková M, Koryta J (1990) Deuterons cannot replace protons in active transport processes in yeast. FEBS Lett 264:203–205
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
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
Lane AN, Fan TW (2015) Regulation of mammalian nucleotide metabolism and biosynthesis. Nucleic Acids Res 43:2466–2485
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
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
Lewis GN (1934) The biology of heavy water. Science 79:151–153
Lewis GN, Cornish RE (1933) Separation of the isotopic forms of water by fractional distillation. J Am Chem Soc 55:2616–2617
MacDonald A, Reed R (1956) The determination of deuterium by the mass-spectrometric method. Analyst 81:401–403
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
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
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
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
Mueller D, Heinzle E (2013) Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures. Curr Opin Biotechnol 24:54–59
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
Olgun A (2007) Biological effects of deuteronation: ATP synthase as an example. Theor Biol Med Model 4:9
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
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
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
Salomonsson L, Branden G, Brzezinski P (2008) Deuterium isotope effect of proton pumping in cytochrome c oxidase. Biochim Biophys Acta 1777:343–350
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
Schwarcz HP, Schoeninger MJ (1991) Stable isotope analyses in human nutritional ecology. Am J Phys Anthropol 34:283–321
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
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
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
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
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
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
Urey HC (1933) The separation and properties of the isotopes of hydrogen. Science 78:566–571
Urey HC, Brickwedde FG, Murphy GM (1932) A hydrogen isotope of mass 2. Phys Rev 39:164–165
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
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
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
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
Washburn EW, Smith ER (1933) The isotopic fractionation of water by distillation and by adsorption. Journ Chem Phys 1:426–426
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
West JB, Bowen GJ, Cerling TE, Ehleringer JR (2006) Stable isotopes as one of nature’s ecological recorders. Trends Ecol Evol 21:408–414
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
Yang J (2016) Deuterium. In: Deuterium: discovery and applications in organic chemistry. Elsevier, Amsterdam
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
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).
Author information
Authors and Affiliations
Corresponding author
Additional information
Dedicated to the memory of Dr. Ivan Šetlík.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12223-019-00740-0