Enzymatic reductive amination of p-hydroxy- and phenylpyruvic acids as a method of synthesis of L-tyrosine and L-phenylalanine labelled with deuterium and tritium

• Autorzy: Pałka K. , Kańska M.
• Języki publikacji: EN

Abstrakty

EN

We report the synthesis of isotopomers of L-phenylalanine and L-tyrosine selectively labelled with hydrogen isotopes in the 2-position of the side chain. The deuterium or tritium label was introduced using reductive amination activity of enzyme L-phenylalanine dehydrogenase (EC 1.4.1.20). This way p-phenylpyruvic acid was converted into [2-2H]-, [2-3H]-, and doubly labelled [2-2H/3H]-isotopomers of L-phenylalanine, using deuteriated, tritiated, and mixed (DTO) incubation media, respectively. Similarly, p-hydroxyphenylpyruvic acid was converted into [2-2H]-, [2-3H]-, and [2-2H/3H]-L-tyrosine. Deuterium labelled isotopomers of L-phenylalanine and --tyrosine can be used as markers in the investigation of abnormal metabolism of these amino acids observed in patients with inborn genetic diseases such as phenylketonuria and tyrosinemia.

Słowa kluczowe

EN

deuterium; enzyme; L-phenylalanine; tritium; L-tyrosine

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2012
• Tom: Vol. 57, No. 3
• Strony: 383--387
• Opis fizyczny: Bibliogr. 16 poz., rys.

Twórcy

autor

Pałka K.

autor

Kańska M.

• Department of Chemistry, University of Warsaw, 1 L. Pasteur Str., 02-093 Warsaw, Poland

Bibliografia

• 1. Asano Y, Yamada A, Kato Y et al. (1990) Enantioselective synthesis of (S)-amino acids by phenylalanine dehydrogenase from Bacillus sphaericus: use of natural and recombinant enzymes. J Org Chem 55:5567–5571
• 2. Augustyniak W, Suchecki P, Jemielity J, Kanski R, Kanska M (2002) Synthesis of tritium labeled isotopomers of L-tyrosine. J Labelled Compd Radiopharm 45:559–567
• 3. Augustyniak W, Suchecki P, Kanski R, Kanska M (2003) Synthesis of carbon and hydrogen isotopomers of L-tyrosine. In: Dean DC, Filer CN, McCarthy KE (eds) Synthesis and applications of isotopocally labelled compounds. Vol. VIII. Wiley, Chichester, pp 235–238
• 4. Brunhuber NMW, Banerjee A, Jacobs WR Jr, Blanchard JS (1984) Cloning, sequencing, and expression of Rhodococcus L-phenylalanine dehydrogenase. J Biol Chem 269:16203–16211
• 5. Brunhuber NMW, Thoden JB, Blanchard JS, Vanhooke JL (2000) Rhodococcus L-phenylalanine dehydrogenase: kinetics, mechanism, and structural basis for catalytic specifity. Biochemistry 39:9174–9187
• 6. Busca P, Paradisi F, Moynihan E, Maguire AR, Engel PC (2004) Enantioselective synthesis of non-natural amino acids using phenylalanine dehydrogenases modified by site-directed mutagenesis. Org Biomol Chem 2:2684–2691
• 7. Gary R, Bates RG, Robinson RA (1964) Second dissociation constant of deuteriophoshoric acid in deuterium oxide from 5 to 50°C: Standardization of pD scale. J Phys Chem 68:3806–3809
• 8. Hummel WE, Schmidt E, Wandrey C, Kula M-R (1986) L-phenylalanine dehydrogenase from Brevibacterium sp. for production of L-phenylalanine by reductive amination of phenylpyruvate. Appl Microbiol Biotechnol 25:175–185
• 9. Kanska M, Boroda E, Augustyniak W, Kanski R (2003) Enzymatic syntheses of aromatic amino acids labeled with carbon and hydrogen isotopes. In: Dean DC, Filer CN, McCarthy KE (eds) Synthesis and applications of isotopocally labelled compounds. Vol. VIII. Wiley, Chichester, pp 141–144
• 10. Mitchell GA, Grompe M, Lambert M, Tanguay RM (2001) Hypertyrosenemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. Vol. II, 8th ed. McGraw-Hill, New York, pp 1777–1785
• 11. Panufnik E, Kanska M (2007) Enzymatic synthesis of isotopomers of tyramine labeled with deuterium and tritium. J Labelled Compd Radiopharm 50:85–89
• 12. Schowen RL (1972) Mechanistic deductions from solvent isotope effects. Prog Phys Org Chem 9:275–332
• 13. Scriver CR (2007) The PAH gene, phenylketonuria, and a paradigm shift. Hum Mutat 28:831–845
• 14. Seah SYK, Britton KL, Rice DW, Asano YP, Engel PC (2002) Single aminoacid substitution in Bacillus sphaericus phenylalanine dehydrogenase dramatically increases its discrimination between phenylalanine and tyrosine substrates. Biochemistry 41:11390–11397
• 15. Seah SYK, Britton KL, Rice DW, Asano Y, Engel PC (2003) Kinetic analysis of phenylalanine dehydrogenase mutants designed for aliphatic amino acid dehydrogenase activity with guidance from homology-based modeling. Eur J Biochem 270:4628–4634
• 16. Sühnel JRL, Schowen LR (1991) Theoretical basis for primary and secondary hydrogen isotope effects. In: Cook PF (ed) Enzyme mechanism from isotope effects. CRS Press, Boca Raton, pp 3–35