Skip to main content
SpringerLink
Log in

Fundamentals and systematics of the non-statistical distributions of isotopes in natural compounds

  • Review
  • Published:
Naturwissenschaften Aims and scope Submit manuscript

An Erratum to this article was published on 20 February 2004

Abstract

The intermolecular and intramolecular non-statistical distribution of the isotopes of the bio-elements in natural compounds must obviously be controlled by logical principles. However, a critical review of the available isotope patterns of natural compounds indicates that a previously discussed general thermodynamic order and its mechanistic foundation cannot satisfactorily explain all experimental data. In the present contribution it is shown that a partial thermodynamic order can eventually be attained for defined positions and compounds under steady-state conditions of metabolism. However, as biological systems are generally open and irreversible, many other in vivo isotope discriminations are dominated by kinetic isotope effects, even in context with reversible reactions. On the other hand, kinetic isotope effects can only become effective in vivo in combination with metabolic branching and the implied isotope shifts of the products are balanced by their relative yields. In vivo, the influences of thermodynamic and kinetic isotope effects are modulated by interferences of the actual metabolic conditions, such as the nature and kind of precursors, alternative metabolic pathways, metabolite pools and fluxes, and by reaction mechanisms. This is demonstrated by giving examples for the isotopes of hydrogen, carbon, nitrogen, oxygen and sulfur, while simultaneously the particularities of the individual elements are elaborated. The resulting general theory of the origin of non-statistical isotope distributions in biological systems permits the interpretation and prediction of isotope patterns and provides the scientific basis for the elucidation of biosyntheses and origin assignments of natural compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Arnelle DR, O’Leary MH (1992) Binding of carbon dioxide to phosphoenolpyruvate carboxykinase deduced from kinetic isotope effects. Biochemistry 31:4363–4368

    CAS  PubMed  Google Scholar 

  • Balabane M, Galimov E, Hermann M, Letolle R (1987) Hydrogen and carbon isotope fractionation during experimental production of bacterial methane. Org Geochem 11:115–119

    Article  CAS  Google Scholar 

  • Beaumont VI, Jahnke LL, Des Marais DJ (2000) Nitrogen isotopic fractionation in the synthesis of photosynthetic pigments in Rhodobacter capsulatus and Anabaena cylindrica. Org Geochem 31:1075–1085

    Article  Google Scholar 

  • Blanco D, Morán MJ, Gutiérrez MD, Moreno J, Dapena E, Mangas J (1992) Biochemical study of the ripening of cider apple varieties. Z Lebensm Unters Forsch 194:33–37

    CAS  Google Scholar 

  • Brenna JT (2001) Natural intramolecular isotope measurements in physiology: elements of the case for an effort toward high-precision position-specific isotope analysis. Rapid Commun Mass Spectrom 15:1252–1262

    Article  CAS  PubMed  Google Scholar 

  • Brooks SPJ (1996) Equilibrium enzymes in metabolic pathways. Biochem Cell Biol 74:411–416

    CAS  PubMed  Google Scholar 

  • Buchachenko AL (2003) Are chemical transformations in an enzyme-substrate complex reversible? The experience of the fractionation of isotopes in enzymatic reactions. Russ J Phys Chem 77:1298–1302

    Google Scholar 

  • Burda K, Bader KP, Schmid GH (2003) 18O isotope effect in the photosynthetic water splitting process. Biochim Biophys Acta 1557:77–82

    Article  CAS  PubMed  Google Scholar 

  • Canfield DE, Thamdrup B (1994) The production of 34S-depleted sulfide during baterial disproportionation of elemental sulfur. Science 266:1973–1975

    CAS  PubMed  Google Scholar 

  • Chang TL, Li WJ (1990) A calibrated measurement of the atomic weight of carbon. Chin Sci Bull 35:290–296

    Google Scholar 

  • Chollet R, Vidal J, O’Leary MH (1996) Phosphoenolpyruvate carboxylase: a ubiquitous, highly regulated enzyme in plants. Annu Rev Plant Physiol Plant Mol Biol 47:273–298

    CAS  Google Scholar 

  • Chu X-L, Ohmoto H (1991) Kinetics of isotope exchange reactions involving intra- and intermolecular reactions. I. Rate law for a system with two chemical compounds and three exchangeable atoms. Geochim Cosmochim Acta 55:1953–1961

    Article  CAS  Google Scholar 

  • Clark JD, O’Keefe SJ, Knowles JR (1988) Malate synthase: proof of a stepwise Claisen condensation using the double-isotope fractionation test. Biochemistry 27:5961–5971

    CAS  PubMed  Google Scholar 

  • DeNiro MJ, Epstein S (1977) Mechanism of carbon isotope fractionation associated with lipid biosynthesis. Science 197:261–263

    CAS  PubMed  Google Scholar 

  • Corso TN, Brenna JT (1997) High precision position-specific isotope analysis. Proc Natl Acad Sci USA 94:1049–1053

    Article  CAS  PubMed  Google Scholar 

  • Farquhar GD, Ehleringer JR, Hubick KT (1989) Carbon isotope discrimination and photosynthesis. Annu Rev Plant Physiol Plant Mol Biol 40:503–537

    CAS  Google Scholar 

  • Fronza G, Fuganti C, Serra S, Cisero M, Koziet J (2002a) Stable isotope labeling pattern of resveratrol and related natural stilbenes. J Agric Food Chem 50:2748–2754

    Article  CAS  PubMed  Google Scholar 

  • Fronza G, Fuganti C, Schmidt H-L, Werner RA (2002b) The δ18O value of the p-OH group of l-tyrosine permits the assignment of its origin to plant or animal sources. Eur Food Res Technol 215:55–58

    Article  CAS  Google Scholar 

  • Galimov EM (1982) Interpretation of isotope fractionation in biological systems. In: Schmidt H-L, Förstel H, Heinzinger K (eds) Stable isotopes: proceedings of the 4th international conference, Jülich, March 23–26, 1981. Elsevier Scientific, Amsterdam, pp 35–47

  • Galimov EM (1985) The biological fractionation of isotopes. Academic Press, London

  • Galimov EM (2003) Isotopic criteria for identification of organic carbon on earth and meteorites. Space Sci Rev 106:249–262

    Article  CAS  Google Scholar 

  • Gillon JS, Yakir D (2000) Naturally low carbonic anhydrase activity in C4 and C3 plants limits discrimination against C18OO during photosynthesis. Plant Cell Environ 23:903–915

    Article  CAS  Google Scholar 

  • Gleixner G, Schmidt H-L (1997) Carbon isotope effects on the fructose-1,6-bisphosphate aldolase reaction: origin for non statistical 13C distributions in carbohydrates. J Biol Chem 272:5382–5387

    Article  CAS  PubMed  Google Scholar 

  • Gleixner G, Schmidt H-L (1998) On-line determination of group specific isotope ratios in model compounds and aquatic humic substances by coupling pyrolysis to GC-C-IRMS. In: Stankowicz BA, Van Bergen PF (eds) Nitrogen containing macromolecules in the bio- and geosphere. (ACS symposia proceedings 707) American Chemical Society, Washington DC, pp 34–46

  • Gleixner G, Scrimgeour C, Schmidt H-L, Viola R (1998) Stable isotope distribution in the major metabolites of source and sink organs of Solanum tuberosum L.: a powerful tool in the study of metabolic partitioning in intact plants. Planta 207:241–245

    Article  CAS  Google Scholar 

  • Gout E, Bligny R, Pascal N, Douce R (1993) 13C nuclear magnetic resonance studies of malate and citrate synthesis and compartmentation in higher plant cells. J Biol Chem 268:3986–3992

    CAS  PubMed  Google Scholar 

  • Guy RD, Fogel ML, Berry JA (1993) Photosynthetic fractionation of the stable isotopes of oxygen and carbon. Plant Physiol 101:37–47

    CAS  PubMed  Google Scholar 

  • Habicht KS, Canfield DE, Rethmeier J (1998) Sulfur isotope fractionation during bacterial reduction and disproportionation of thiosulfate and sulfite. Geochim Cosmochim Acta 62:2585–2595

    Article  CAS  Google Scholar 

  • Handley LL, Raven JA (1992) The use of natural abundance of nitrogen isotopes in plant physiology and ecology. Plant Cell Environ 15:965–985

    CAS  Google Scholar 

  • Hayes JM (1993) Factors controlling 13C contents of sedimentary organic compounds: principles and evidence. Mar Geol 113:111–125

    Article  CAS  Google Scholar 

  • Hayes JM (2001) Fractionation of the isotopes of carbon and hydrogen in biosynthetic processes. In: Valley JW, Cole DR (eds) Stable isotope geochemistry. (Reviews in mineralogy and geochemistry, vol. 43) Mineralogical Society of America, Washington DC, pp 225–277

  • Hoefs J (1997) Stable isotope geochemistry, 4th edn. Springer, Berlin Heidelberg New York, pp 59–60, 137

  • Ivlev AA (2001) Carbon isotope effects (13C/12C) in biological systems. Sep Sci Technol 36:1819–1914

    Article  CAS  Google Scholar 

  • Jux A, Gleixner G, Boland W (2001) Classification of terpenoids according to the methylerythritolphosphate or the mevalonate pathway with natural 12C/13C isotope ratios: dynamic allocation of resources in induced plants. Angew Chem Int Edn 40:2091–2093

    Article  CAS  Google Scholar 

  • Kurz LC, Nakra T, Stein R, Plungkhen W, Riley M., Hsu F, Drysdale GR (1998) Effects of changes in three catalytic residues on the relative stabilities of some of the intermediates and transition states in the citrate synthase reaction. Biochemistry 37:9724–9737

    CAS  PubMed  Google Scholar 

  • Kurz LC, Drysdale G, Riley M, Tomar MA, Chen J, Russell RJM, Danson MJ (2000) Kinetics and mechanism of the citrate synthase from the thermophilic archaeon Thermoplasma acidophilum. Biochemistry 39:2283–2296

    CAS  PubMed  Google Scholar 

  • Lance C, Rustin P (1984) The central role of malate in plant metabolism. Physiol Veg 22:625–641

    CAS  Google Scholar 

  • Martin ML, Martin GJ (1991) Deuterium NMR in the study of site-specific natural isotope fractionation (SNIF-NMR). In: Diehl P, Fluck E, Günther H, Kosfeld R, Seelig J (Eds) NMR Basic Principles and Progress. Springer, Berlin, pp 1–61

  • Martin GJ, Martin ML (1999) Thirty years of flavor NMR. In: Teranishi R, Wick EL, Hornstein I (eds) Flavor chemistry: thirty years of progress. Kluwer/Plenum, New York, pp 19–30

  • Martin GJ, Martin ML, Mabon F, Bricout J (1982) A new method for the identification of the origin of natural products: quantitative 2H NMR at the natural abundance level applied to the characterisation of anetholes. J Am Chem Soc 104:2658–2659

    CAS  Google Scholar 

  • Masud Z, Vallet C, Martin GJ (1999) Stable isotope characterisation of milk components and whey ethanol. J Agric Food Chem 47:4693–4699

    Article  CAS  PubMed  Google Scholar 

  • Meinschein WG, Hegemann GD, Bromley BW (1984) Intramolecular distribution of stable isotopes of carbon. In: Abstract 17th international geology congress, vol 5. Moscow, pp 345–346 (cited by Galimov 2003)

  • Melzer E, O’Leary MH (1987) Anapleurotic CO2 fixation by phosphoenolpyruvate carboxylase in C3 plants. Plant Physiol 84:58–60

    CAS  Google Scholar 

  • Melzer E, Schmidt H-L (1987) Carbon isotope effects on the pyruvate dehydrogenase reaction and their importance for relative carbon-13 depletions in lipids. J Biol Chem 262:8159–8164

    CAS  PubMed  Google Scholar 

  • Monson KD, Hayes JM (1982a) Biosynthetic control of the natural abundance of carbon 13 at specific positions within fatty acids in Saccharomyces cerevisiae. J Biol Chem 257:5568–5575

    CAS  PubMed  Google Scholar 

  • Monson KD, Hayes JM (1982b) Carbon isotopic fractionation in the biosynthesis of bacterial fatty acids: ozonolysis of unsaturated fatty acids as a means of determining the intramolecular distribution of carbon isotopes. Geochim Cosmochim Acta 46:139–149

    Article  CAS  Google Scholar 

  • Mulholland AJ, Richards WG (1998) Modeling enzyme reaction intermediates and transition states: citrate synthase. J Phys Chem B 102:6635–6646

    Article  CAS  Google Scholar 

  • Northrop DB (2002) Effects of high pressure on enzymatic activity. Biochim Biophys Acta 1595:71–79

    Article  CAS  PubMed  Google Scholar 

  • O’Leary MH (1988) Carbon isotopes in photosynthesis. Bioscience 38:328–336

    CAS  Google Scholar 

  • O’Leary MH (1993) Biochemical basis of carbon isotope fractionation. In: Ehleringer JR, Hall AE, Farquhar GD (eds) Stable isotopes and plant–water relations. Academic Press, San Diego, pp 19–28

  • Olleros-Izard T (1983) Kinetische Isotopeneffekte der Arginase- und der Nitratreduktase-Reaktion. PHD thesis, Technische Universität München, Freising-Weihenstephan, Germany

  • Ovádi J (1991) Physiological significance of metabolic channelling. J Theor Biol 152:1–22

    Google Scholar 

  • Polyakov VB, Mineev SD (2000) The use of Mössbauer spectroscopy in stable isotope geochemistry. Geochim Cosmochim Acta 64:849–865

    Article  CAS  Google Scholar 

  • Richter G (1996). Biochemie der Pflanzen. Georg Thieme, Stuttgart, pp 147–148

  • Rinaldi G, Meinschein WG, Hayes JM (1974) Intramolecular carbon isotopic distribution in biologically produced acetoin. Biomed Mass Spectrom 1:415–417

    CAS  PubMed  Google Scholar 

  • Rishavy MA, Cleland WW (1999) 13C, 15N, and 18O equilibrium isotope effects and fractionation factors. Can J Chem 77:967–977

    Article  CAS  Google Scholar 

  • Roßmann A (2001) Determination of stable isotope ratios in food analysis. Food Rev Int 17:347–381

    CAS  Google Scholar 

  • Roßmann A, Schmidt H-L (1989) Nachweis der Herkunft von Ethanol und der Zuckerung von Wein durch positionelle Wasserstoff- und Kohlenstoff-Isotopenverhältnismessung. Z Lebensm Unters Forsch 188:434–438

    Google Scholar 

  • Roßmann A, Butzenlechner M, Schmidt H-L (1991) Evidence for a nonstatistical carbon isotope distribution in natural glucose. Plant Physiol 96:609–614

    Google Scholar 

  • Schleucher J (1998) Intramolecular deuterium distribution and plant growth conditions. In: Griffiths H (ed) Stable isotopes: integration of biological, ecological and geochemical processes. BIOS Scientific, Oxford, pp 63–73

  • Schleucher J, Vanderveer P, Markley JL, Sharkey TD (1999) Intramolecular deuterium distributions reveal disequilibrium of chloroplast phosphoglucose isomerase. Plant Cell Environ 22:525–533

    Article  CAS  Google Scholar 

  • Schmidt H-L (1999) Isotope discriminations upon biosynthesis in natural systems: general causes and individual factors of the different bioelements. Isot Environ Health Stud 35:11–18

    CAS  Google Scholar 

  • Schmidt H-L (2001) Fundamentals, prerequisites and realisations of in vivo non-statistical isotope distributions in natural compounds. In: Abstracts, 1st international symposium on isotopomers (ISI), Yokohama, Japan 2001. Japan Science and Technology Corporation (JST), Yokohama, pp 49–50

  • Schmidt H-L, Eisenreich W (2001) Systematic and regularities in the origin of 2H-patterns in natural compounds. Isot Environ Health Stud 37:253–254

    CAS  Google Scholar 

  • Schmidt H-L, Gleixner G (1998) Carbon isotope effects on key reactions in plant metabolism and 13C-patterns in natural compounds. In: Griffiths H (ed) Stable isotopes, integration of biological, ecological and geochemical processes. BIOS Scientific, Oxford, pp 13–25

  • Schmidt H-L, Kexel H (1998) Metabolite pools and metabolic branching as factors of in vivo isotope discriminations by kinetic isotope effects. Isot Environ Health Stud 34:19–30

    CAS  Google Scholar 

  • Schmidt H-L, Kexel H, Butzenlechner M, Schwarz S, Gleixner G, Thimet S, Werner RA, Gensler M (1995) Non-statistical isotope distribution in natural compounds: mirror of their biosynthesis and key for their origin assignment. In: Wada E, Yoneyama T, Minagawa M, Ando T, Fry BD (eds) Stable isotopes in the biosphere. Kyoto University Press, Japan, pp 17–35

  • Schmidt H-L, Roßmann A, Werner RA (1998) Stable isotope ratio analysis in quality control of flavourings. In: Ziegler E, Ziegler H (eds) Flavourings: production, composition, applications, regulations. Wiley-VCH, Weinheim, pp 539–594

  • Schmidt H-L, Gensler M, Weber D (2000) Nachweis eines unerlaubten Zusatzes von naturidentischen Säuren zu Obstsäften mit Hilfe von Isotopenverhältnismessungen. Fluess Obst 67:131–136

    CAS  Google Scholar 

  • Schmidt H-L, Werner RA, Roßmann A (2001) 18O-pattern and biosynthesis of natural plant products. Phytochemistry 58:9–32

    Article  CAS  PubMed  Google Scholar 

  • Schmidt H-L, Werner RA, Eisenreich W (2003) Systematics of 2H-patterns in natural compounds and its importance for the elucidation of biosynthetic pathways. Phytochem Rev 2

  • Sessions AL, Burgoyne TW, Schimmelmann A, Hayes JM (1999) Fractionation of hydrogen isotopes in lipid biosynthesis. Org Geochem 30:1193–1200

    Article  CAS  Google Scholar 

  • Stein LY, Yung YL (2003) Production, isotope composition, and atmospheric fate of biologically produced nitrous oxide. Annu Rev Earth Planet Sci 31:3529–356

    Google Scholar 

  • Sternberg L, DeNiro MJ (1983) Biogeochemical implications of the isotope equilibrium fractionation factor between the oxygen atoms of acetone and water. Geochim Cosmochim Acta 47:2271–2274

    Article  CAS  Google Scholar 

  • Sumegi B, Sherry AD, Malloy CR, Evans C, Srere PA (1991). Is there tight channelling in the tricarboxylic acid cycle metabolon? Biochem Soc Trans 19:1002–1005

    CAS  PubMed  Google Scholar 

  • Thode HG (1991) Sulfur isotopes in nature and the environment: an overview. In: Krouse HR, Grinenko VA (eds) SCOPE 43. Stable isotopes: natural and anthropogenic sulfur in the environment. Wiley, Chichester, pp 1–21

    Google Scholar 

  • Toyoda S, Yoshida N, Tatsuya M, Miwa T, Matsui Y, Yamagishi H, Tsunogai U, Nojiri Y, Tsurushima N (2002) Production mechanism and global budget of N2O inferred from its isotopomers in the western North Pacific. Geophys Res Lett 29(3):7-1–7-4

    Article  Google Scholar 

  • Voet D, Voet JG (1992) Biochemie. VCH, Weinheim, Germany

  • Wasser IM, Vries S de, Moenne-Loccoz, Schröder I, Karlin KD (2002) Nitric oxide in biological denitrification: Fe/Cu metalloenzyme and metal complex NOx redox chemistry. Chem Rev 102:1201–1234

    Article  CAS  PubMed  Google Scholar 

  • Weber D, Kexel H, Schmidt H-L (1997) 13C-pattern of natural glycerol: origin and practical importance. J Agric Food Chem 45:2042–2046

    Article  CAS  Google Scholar 

  • Werner RA, Schmidt H-L (2002) The in vivo nitrogen isotope discrimination among organic plant compounds. Phytochemistry 61:465–484

    Article  CAS  PubMed  Google Scholar 

  • Yoneyama T, Kamachi K, Yamaya T, Mae T (1993) Fractionation of nitrogen isotopes by glutamine synthetase isolated from spinach leaves. Plant Cell Physiol 34:489–491

    CAS  Google Scholar 

  • Zhang B-L, Billault I, Li X, Mabon F, Remaud G, Martin ML (2002) Hydrogen isotopic profile in the characterisation of sugars: influence of the metabolic pathway. J Agric Food Chem 50:1574–1580

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks Eric M. Galimov, Moscow, for valuable and fruitful discussions on aspects of the thermodynamic order; Helmut Simon, München, for discussions on the reversibility and irreversibility of biochemical systems; Roland A. Werner for providing the references and helping with the manuscript; Manfred Gensler for contributing unpublished experimental data on citric and malic acid 13C-patterns; and his wife Elis for her patience with and her understanding of his viewpoint on “retirement”.

Author information

Author notes

  1. Hanns-Ludwig Schmidt

    Present address: Prielhofweg 2, 84036, Landshut, Germany

Authors and Affiliations

  1. Lehrstuhl für Biologische Chemie, Technische Universität München, 85350, Freising-Weihenstephan, Germany

    Hanns-Ludwig Schmidt

Authors
  1. Hanns-Ludwig Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanns-Ludwig Schmidt.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00114-004-0505-0

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmidt, HL. Fundamentals and systematics of the non-statistical distributions of isotopes in natural compounds. Naturwissenschaften 90, 537–552 (2003). https://doi.org/10.1007/s00114-003-0485-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00114-003-0485-5

Keywords

Search

Navigation