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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 13, pp 2891–2904 | Cite as

Simultaneous extraction and determination of mono-/polyglutamyl folates using high-performance liquid chromatography-tandem mass spectrometry and its applications in starchy crops

  • Xing Wan
  • Li-Da Han
  • Min Yang
  • Hong-Yang Zhang
  • Chun-Yi ZhangEmail author
  • Ping HuEmail author
Research Paper

Abstract

Folates are typically present in polyglutamyl form in organisms. In traditional extraction methods, polyglutamyl folates are hydrolyzed to monoglutamates, sacrificing valuable information. To advance folate metabolism research, we developed an accurate, sensitive, and reproducible extraction method for polyglutamyl folate species in maize, the main crop in most parts of the world. Twelve folates, including six polyglutamyl folates, were simultaneously determined in maize for the first time using high-performance liquid chromatography-tandem mass spectrometry. The glutamation states of the folates were protected by boiling, which inactivated the native conjugases. α-Amylase and protease were added to obtain better recoveries and decrease difficulties in centrifugation and filtration. The recoveries (n = 5) of six polyglutamyl folates were between 80.5 and 101%. All calibration curves showed good linear regression (r2 ≥ 0.994) within the working range. The instrumental limits of detection and quantitation ranged from 0.070 to 2.4 ng/mL and 0.22 to 8.0 ng/mL, respectively. Intra- and inter-day precision was below 7.81% and 11.9%, respectively (n = 5). Using this method, changes in poly- and monoglutamyl folates during maize germination were determined for the first time. The results suggest that folates were largely synthesized as germination initiated, and 5-methyltetrahydrofolate was the most abundant species. Tetraglutamyl 5-methyltetrahydrofolate contributed more than 50% of the 5-methyltetrahydrofolate species. Inverse changes in contents of 5,10-methenyltetrahydrofolate, and 10-formyl folic acid, monoglutamate, and diglutamate of 5-formyltetrahydrofolate were also observed, indicating potential regulation. Additionally, polyglutamyl folates in sweet potatoes were determined using this method, indicating its applications in starchy crops.

Keywords

Polyglutamyl 5-formyltetrahydrofolate Polyglutamyl 5-methyltetrahydrofolate Folate quantification High-performance liquid chromatography-tandem mass spectrometry Starchy crops Maize germination 

Notes

Acknowledgments

This work was supported by the Collaborative Innovation Action, Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences [CAAS-XTCX2016009], Agriculture Applied Technology Development Program (Z20180103) and Fundamental Research Funds For Central Non-Profit Scientific Insitution. The researches were conducted in the Central Laboratory of Biotechnology Research Institute, Chinese Academy of Agricultural Science.

Funding information

This work was supported by the Collaborative Innovation Action, Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences [CAAS-XTCX2016009], Agriculture Applied Technology Development Program (Z20180103) and Fundamental Research Funds For Central Non-Profit Scientific Insitution.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

216_2019_1742_MOESM1_ESM.pdf (344 kb)
ESM 1 (PDF 343 kb)

References

  1. 1.
    Fabrice RB, StéPhane R, Samuel J, Roland D, Sergei S, Dominiquevander S. Folates in plants: biosynthesis, distribution, and enhancement. Physiol Plant. 2006;126(3):330–42.  https://doi.org/10.1111/j.1399-3054.2005.00587.x.CrossRefGoogle Scholar
  2. 2.
    Shane B. Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vitam Horm. 1989;45:263–335.  https://doi.org/10.1016/S0083-6729(08)60397-0.CrossRefGoogle Scholar
  3. 3.
    Brzezinska A, Winska P, Balinska M. Cellular aspects of folate and antifolate membrane transport. Acta Biochim Pol. 2000;47(3):735–49.Google Scholar
  4. 4.
    Ravanel S, Block MA, Rippert P, Jabrin S, Curien G, Rebeille F, et al. Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol. J Biol Chem. 2004;279(21):22548–57.  https://doi.org/10.1074/jbc.M313250200.CrossRefGoogle Scholar
  5. 5.
    Besson V, Rebeille F, Neuburger M, Douce R, Cossins EA. Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria. Biochem J. 1993;292(Pt 2):425–30.  https://doi.org/10.1042/bj2920425.CrossRefGoogle Scholar
  6. 6.
    Rebeille F, Neuberger M, Douce R. Interaction between glycine decarboxylase, serine hydroxymethyltransferase and tetrahydrofolate polyglutamates in pea leaf mitochondria. Biochem J. 1994;302(1):223–8.  https://doi.org/10.1042/bj3020223.CrossRefGoogle Scholar
  7. 7.
    Scott J, Rebeille F, Fletcher J. Folic acid and folates: the feasibility for nutritional enhancement in plant foods. J Sci Food Agric. 2000;80(7):795–824.  https://doi.org/10.1002/(Sici)1097-0010(20000515)80:7<795::Aid-Jsfa599>3.3.Co;2-B.CrossRefGoogle Scholar
  8. 8.
    Groth M, Moissiard G, Wirtz M, Wang H, Garcia-Salinas C, Ramos-Parra PA, et al. MTHFD1 controls DNA methylation in Arabidopsis. Nat Commun. 2016;7:11640.  https://doi.org/10.1038/ncomms11640.CrossRefGoogle Scholar
  9. 9.
    Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. Quantitative flux analysis reveals folate-dependent NADPH production. Nature. 2014;510(7504):298–302.  https://doi.org/10.1038/nature13236.CrossRefGoogle Scholar
  10. 10.
    Joubert BR, den Dekker HT, Felix JF, Bohlin J, Ligthart S, Beckett E, et al. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns. Nat Commun. 2016;7:10577.  https://doi.org/10.1038/ncomms10577.CrossRefGoogle Scholar
  11. 11.
    Bekaert S, Storozhenko S, Mehrshahi P, Bennett MJ, Lambert W, Gregory JF 3rd, et al. Folate biofortification in food plants. Trends Plant Sci. 2008;13(1):28–35.  https://doi.org/10.1016/j.tplants.2007.11.001.CrossRefGoogle Scholar
  12. 12.
    Kim SE, Hinoue T, Kim MS, Sohn KJ, Cho RC, Weisenberger DJ, et al. Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells. J Nutr Biochem. 2016;29:27–35.  https://doi.org/10.1016/j.jnutbio.2015.10.019.CrossRefGoogle Scholar
  13. 13.
    Strobbe S, Van Der Straeten D. Folate biofortification in food crops. Curr Opin Biotechnol. 2017;44:202–11.  https://doi.org/10.1016/j.copbio.2016.12.003.CrossRefGoogle Scholar
  14. 14.
    Blancquaert D, De Steur H, Gellynck X, Van Der Straeten D. Present and future of folate biofortification of crop plants. J Exp Bot. 2014;65(4):895–906.  https://doi.org/10.1093/jxb/ert483.CrossRefGoogle Scholar
  15. 15.
    Yu S, Tian L. Breeding major cereal grains through the lens of nutrition sensitivity. Mol Plant. 2018;11(1):23–30.  https://doi.org/10.1016/j.molp.2017.08.006.CrossRefGoogle Scholar
  16. 16.
    Blancquaert D, Van Daele J, Strobbe S, Kiekens F, Storozhenko S, De Steur H, et al. Improving folate (vitamin B-9) stability in biofortified rice through metabolic engineering. Nat Biotechnol. 2015;33(10):1076.  https://doi.org/10.1038/nbt.3358.CrossRefGoogle Scholar
  17. 17.
    Zhou HR, Zhang FF, Ma ZY, Huang HW, Jiang L, Cai T, et al. Folate polyglutamylation is involved in chromatin silencing by maintaining global DNA methylation and histone H3K9 dimethylation in Arabidopsis. Plant Cell. 2013;25(7):2545–59.  https://doi.org/10.1105/tpc.113.114678.CrossRefGoogle Scholar
  18. 18.
    Srivastava AC, Chen F, Ray T, Pattathil S, Pena MJ, Avci U, et al. Loss of function of folylpolyglutamate synthetase 1 reduces lignin content and improves cell wall digestibility in Arabidopsis. Biotechnol Biofuels. 2015;8:224.  https://doi.org/10.1186/s13068-015-0403-z.CrossRefGoogle Scholar
  19. 19.
    Jiang L, Liu Y, Sun H, Han Y, Li J, Li C, et al. The mitochondrial folylpolyglutamate synthetase gene is required for nitrogen utilization during early seedling development in arabidopsis. Plant Physiol. 2013;161(2):971–89.  https://doi.org/10.1104/pp.112.203430.CrossRefGoogle Scholar
  20. 20.
    Srivastava AC, Ramos-Parra PA, Bedair M, Robledo-Hernandez AL, Tang Y, Sumner LW, et al. The folylpolyglutamate synthetase plastidial isoform is required for postembryonic root development in Arabidopsis. Plant Physiol. 2011;155(3):1237–51.  https://doi.org/10.1104/pp.110.168278.CrossRefGoogle Scholar
  21. 21.
    Altic L, McNulty H, Hoey L, McAnena L, Pentieva K. Validation of folate-enriched eggs as a functional food for improving folate intake in consumers. Nutrients. 2016;8(12). doi: https://doi.org/10.3390/nu8120777.
  22. 22.
    Maharaj PP, Prasad S, Devi R, Gopalan R. Folate content and retention in commonly consumed vegetables in the South Pacific. Food Chem. 2015;182:327–32.  https://doi.org/10.1016/j.foodchem.2015.02.096.CrossRefGoogle Scholar
  23. 23.
    Devi R, Arcot J, Sotheeswaran S, Ali S. Folate contents of some selected Fijian foods using tri-enzyme extraction method. Food Chem. 2008;106(3):1100–4.  https://doi.org/10.1016/j.foodchem.2007.07.037.CrossRefGoogle Scholar
  24. 24.
    Goyer A, Navarre DA. Determination of folate concentrations in diverse potato germplasm using a trienzyme extraction and a microbiological assay. J Agric Food Chem. 2007;55(9):3523–8.  https://doi.org/10.1021/jf063647x.CrossRefGoogle Scholar
  25. 25.
    Wang C, Riedl KM, Schwartz SJ. A liquid chromatography-tandem mass spectrometric method for quantitative determination of native 5-methyltetrahydrofolate and its polyglutamyl derivatives in raw vegetables. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(29):2949–58.  https://doi.org/10.1016/j.jchromb.2010.08.043.CrossRefGoogle Scholar
  26. 26.
    Campos-Gimenez E, Benet S, Oguey Y, Martin F, Redeuil K. The contribution of minor folates to the total vitamin B9 content of Infant formula and clinical nutrition products. Food Chem. 2018;249:91–7.  https://doi.org/10.1016/j.foodchem.2017.12.061.CrossRefGoogle Scholar
  27. 27.
    van Haandel L, Becker ML, Williams TD, Stobaugh JF, Leeder JS. Comprehensive quantitative measurement of folate polyglutamates in human erythrocytes by ion pairing ultra-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2012;26(14):1617–30.  https://doi.org/10.1002/rcm.6268.CrossRefGoogle Scholar
  28. 28.
    Ogwang S, Nguyen HT, Sherman M, Bajaksouzian S, Jacobs MR, Boom WH, et al. Bacterial conversion of folinic acid is required for antifolate resistance. J Biol Chem. 2011;286(17):15377–90.  https://doi.org/10.1074/jbc.M111.231076.CrossRefGoogle Scholar
  29. 29.
    Schittmayer M, Birner-Gruenberger R, Zamboni N. Quantification of cellular folate species by LC-MS after stabilization by derivatization. Anal Chem. 2018;90(12):7349–56.  https://doi.org/10.1021/acs.analchem.8b00650.CrossRefGoogle Scholar
  30. 30.
    de la Garza RD, Quinlivan EP, Klaus SMJ, Basset GJC, Gregory JF, Hanson AD. Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis. Proc Natl Acad Sci U S A. 2004;101(38):13720–5.CrossRefGoogle Scholar
  31. 31.
    Orsomando G, de la Garza RD, Green BJ, Peng M, Rea PA, Ryan TJ, et al. Plant gamma-glutamyl hydrolases and folate polyglutamates: characterization, compartmentation, and co-occurrence in vacuoles. J Biol Chem. 2005;280(32):28877–84.  https://doi.org/10.1074/jbc.M504306200.CrossRefGoogle Scholar
  32. 32.
    Ramos-Parra PA, Garcia-Salinas C, Hernandez-Brenes C, de la Garza RI. Folate levels and polyglutamylation profiles of papaya (Carica papaya cv. Maradol) during fruit development and ripening. J Agric Food Chem. 2013;61(16):3949–56.  https://doi.org/10.1021/jf305364x.CrossRefGoogle Scholar
  33. 33.
    Upadhyaya P, Tyagi K, Sarma S, Tamboli V, Sreelakshmi Y, Sharma R. Natural variation in folate levels among tomato (Solanum lycopersicum) accessions. Food Chem. 2017;217:610–9.  https://doi.org/10.1016/j.foodchem.2016.09.031.CrossRefGoogle Scholar
  34. 34.
    Van Daele J, Blancquaert D, Kiekens F, Van Der Straeten D, Lambert WE, Stove CP. Folate profiling in potato (Solanum tuberosum) tubers by ultrahigh-performance liquid chromatography-tandem mass spectrometry. J Agric Food Chem. 2014;62(14):3092–100.  https://doi.org/10.1021/jf500753v.CrossRefGoogle Scholar
  35. 35.
    De Brouwer V, Storozhenko S, Van de Steene JC, Wille SMR, Stove CP, Van Der Straeten D, et al. Optimisation and validation of a liquid chromatography-tandem mass spectrometry method for folates in rice. J Chromatogr A. 2008;1215(1–2):125–32.  https://doi.org/10.1016/j.chroma.2008.11.004.CrossRefGoogle Scholar
  36. 36.
    European Medicines Agency. Bioanalytical method validation. https://www.ema.europa.eu/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf. Accessed 22 Dec. 2018.
  37. 37.
    McKillop DJ, Pentieva KD, Scott JM, Strain JJ, McCreedy R, Alexander J, et al. Protocol for the production of concentrated extracts of food folate for use in human bioavailability studies. J Agric Food Chem. 2003;51(15):4382–8.  https://doi.org/10.1021/jf0262312.CrossRefGoogle Scholar
  38. 38.
    Tyagi K, Upadhyaya P, Sarma S, Tamboli V, Sreelakshmi Y, Sharma R. High performance liquid chromatography coupled to mass spectrometry for profiling and quantitative analysis of folate monoglutamates in tomato. Food Chem. 2015;179:76–84.CrossRefGoogle Scholar
  39. 39.
    Fazili Z, Pfeiffer CM. Accounting for an isobaric interference allows correct determination of folate Vitamers in serum by isotope dilution-liquid chromatography-tandem MS. J Nutr. 2013;143(1):108–13.  https://doi.org/10.3945/jn.112.166769.CrossRefGoogle Scholar
  40. 40.
    Shohag MJ, Wei Y, Yang X. Changes of folate and other potential health-promoting phytochemicals in legume seeds as affected by germination. J Agric Food Chem. 2012;60(36):9137–43.  https://doi.org/10.1021/jf302403t.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina
  2. 2.Biotechnology Research InstituteChinese Academy of Agricultural SciencesBeijingChina

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