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.
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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
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
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
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
Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics Mass spectrometry reviews 26:51–78
Gronwald W et al (2008) Urinary metabolite quantification employing 2D NMR spectroscopy. Anal Chem 80:9288–9297
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
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
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
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
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
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
Robertson DG (2005) Metabonomics in toxicology: a review. Toxicol Sci 85:809–822
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
Tada KWY, Arakawa T (1967) Hypervalinemia. Its metabolic lesion and therapeutic approach. Am J Dis Child 113:64–67
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
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
Wishart DS (2008) Applications of metabolomics in drug discovery and development. Drugs R&D 9:307–322
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.
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Handling Editor: D. Tsikas.
S. Ghosh and A. Sengupta are equally contributed to this work.
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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
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DOI: https://doi.org/10.1007/s00726-015-1994-1