Skip to main content
Log in

Quantitative metabolic profiling of NMR spectral signatures of branched chain amino acids in blood serum

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Branched Chain Amino Acids (BCAAs) are related to different aspects of diseases like pathogenesis, diagnosis and even prognosis. While in some diseases, levels of all the BCAAs are perturbed; in some cases, perturbation occurs in one or two while the rest remain unaltered. In case of ischemic heart disease, there is an enhanced level of plasma leucine and isoleucine but valine level remains unaltered. In ‘Hypervalinemia’, valine is elevated in serum and urine, but not leucine and isoleucine. Therefore, identification of these metabolites and profiling of individual BCAA in a quantitative manner in body-fluid like blood plasma/serum have long been in demand. 1H NMR resonances of the BCAAs overlap with each other which complicates quantification of individual BCAAs. Further, the situation is limited by the overlap of broad resonances of lipoprotein with the resonances of BCAAs. The widely used commercially available kits cannot differentially estimate the BCAAs. Here, we have achieved proper identification and characterization of these BCAAs in serum in a quantitative manner employing a Nuclear Magnetic Resonance-based technique namely T2-edited Correlation Spectroscopy (COSY). This approach can easily be extended to other body fluids like bile, follicular fluids, saliva, etc.

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

Access this article

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

  • Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL (1996) Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 171:221–226

    Article  CAS  PubMed  Google Scholar 

  • Blomstrand E, Celsing F, Newsholme EA (1988) Changes in plasma concentrations of aromatic and branched-chain amino acids during sustained exercise in man and their possible role in fatigue Acta physiologica. Scandinavica 133:115–121

    Article  CAS  Google Scholar 

  • Crandall EA, Fernstrom JD (1983) Effect of experimental diabetes on the levels of aromatic and branched-chain amino acids in rat blood and brain. Diabetes 32:222–230

    Article  CAS  PubMed  Google Scholar 

  • De Luca V, Viggiano E, Messina G, Viggiano A, Borlido C, Viggiano A, Monda M (2008) Peripheral amino acid levels in schizophrenia and antipsychotic treatment. Psychiatry Investig 5:203–208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics Mass spectrometry reviews 26:51–78

    Article  CAS  PubMed  Google Scholar 

  • Gronwald W et al (2008) Urinary metabolite quantification employing 2D NMR spectroscopy. Anal Chem 80:9288–9297

    Article  CAS  PubMed  Google Scholar 

  • Harris RA et al (1990) Regulation of the branched-chain alpha-ketoacid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease. Adv Enzyme Regul 30:245–263

    Article  CAS  PubMed  Google Scholar 

  • Hu K, Westler WM, Markley JL (2007a) Simultaneous quantification and identification of individual chemicals in metabolite mixtures by two-dimensional extrapolated time-zero (1)H-(13)C HSQC (HSQC(0)). J Am Chem Soc 133:1662-1665

  • Hu F, Furihata K, Kato Y, Tanokura M (2007b) Nondestructive quantification of organic compounds in whole milk without pretreatment by two-dimensional NMR spectroscopy. J Agric Food Chem 55:4307–4311

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Zhou M, Sun H, Wang Y (2011) Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit? Cardiovasc Res. doi:10.1093/cvr/cvr070

    Google Scholar 

  • Ludwig C, Viant MR (2010) Two-dimensional J-resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox. Phytochem Anal 21:22–32. doi:10.1002/pca.1186

    Article  CAS  PubMed  Google Scholar 

  • Nicholson JK, Holmes E, Elliott P (2008) The metabolome-wide association study: a new look at human disease risk factors. J Proteome Res 7:3637–3638

    Article  CAS  PubMed  Google Scholar 

  • Rai RK, Tripathi P, Sinha N (2009) Quantification of metabolites from two-dimensional nuclear magnetic resonance spectroscopy: application to human urine samples. Anal Chem 81:10232–10238

    Article  CAS  PubMed  Google Scholar 

  • Robertson DG (2005) Metabonomics in toxicology: a review. Toxicol Sci 85:809–822

    Article  CAS  PubMed  Google Scholar 

  • Saito T, Kobatake K, Ozawa H, Ogata M (1994) Aromatic and branched-chain amino acid levels in alcoholics. Alcohol and alcoholism (Oxford, Oxfordshire) 29:133–135

  • Sasi P et al (2007) Metabolic acidosis and other determinants of hemoglobin-oxygen dissociation in severe childhood Plasmodium falciparum malaria. Am J Trop Med Hyg 77:256–260

    CAS  PubMed  Google Scholar 

  • Tada KWY, Arakawa T (1967) Hypervalinemia. Its metabolic lesion and therapeutic approach. Am J Dis Child 113:64–67

    Article  CAS  PubMed  Google Scholar 

  • Tang H, Wang Y, Nicholson JK, Lindon JC (2004) Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma. Anal Biochem 325:260–272

    Article  CAS  PubMed  Google Scholar 

  • Williams PG, Saunders JK, Dyne M, Mountford CE, Holmes KT (1988) Application of a T2-filtered COSY experiment to identify the origin of slowly relaxing species in normal and malignant tissue. Magn Reson Med 7:463–471

    Article  CAS  PubMed  Google Scholar 

  • Wishart DS (2008) Applications of metabolomics in drug discovery and development. Drugs R&D 9:307–322

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The financial support by DST and TIFR is gratefully acknowledged. KC acknowledges DST Inspire Faculty fellowship for providing financial support. AS acknowledges Council of Scientific and Industrial Research, Government of India for providing SPM Fellowship. KC acknowledges the NMR facility provided by TIFR, Mumbai and JKU, Linz.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kousik Chandra.

Additional information

Handling Editor: D. Tsikas.

S. Ghosh and A. Sengupta are equally contributed to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 151 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghosh, S., Sengupta, A. & Chandra, K. Quantitative metabolic profiling of NMR spectral signatures of branched chain amino acids in blood serum. Amino Acids 47, 2229–2236 (2015). https://doi.org/10.1007/s00726-015-1994-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-015-1994-1

Keywords

Navigation