Stereochemical Studies on the Metabolism of Amino Acids

  • D. J. Aberhart
Part of the Recent Advances in Phytochemistry book series (RAPT, volume 13)


This chapter is devoted to the discussion of two topics concerning the stereochemistry of the metabolism of branched-chain amino acids. First we will review our work on the stereochemistry of the biosynthesis of penicillins from valine in Penicillium chrysogenum. The second topic will be the stereochemistry of certain steps in the degradative metabolism of L-valine and L-leucine in several organisms.


Amino Acid Metabolism Penicillium Chrysogenum Isobutyric Acid Unlabeled Sample Methylmalonic Acidemia 
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  1. 1.
    Arnstein, H.R.V. and D. Morris. 1960. The Structure of a Peptide Containing a-Aminoadipic Acid, Cystine, and Valine, Present in the Mycelium of Penicillin chrysogenum. Biochem. J. 76:357–361.Google Scholar
  2. 2.
    Loder, P.B. and E.P. Abraham. 1971. Isolation and Nature of Intracellular Peptides from a Cephalosporin C-Producing Cephalosporium sp. Biochem. J. 123:471–476.Google Scholar
  3. 3.
    Fawcett, P. A., P. B. Loder, M. J. Duncan, T. J. Beesley, and E. P. Abraham. 1973. Formation and Properties of Protoplasts from Antibiotic-producing Strains of Penicillium chrysogenum and Cephalosporium acremonium. J. Gen. Microbiol.79:293–309.PubMedGoogle Scholar
  4. 4.
    Aberhart, D. J. 1977. Biosynthesis of 3-Lactam Antibiotics. Tetrahedron, 33:1545–1559.CrossRefGoogle Scholar
  5. 5.
    Cooper, R. D. G., and D. O. Spry. 1972. Rearrangements of Cephalosporins and Penicillins. In Cephalosporins and Penicillins, Chemistry and Biology, E. H. Flynn, ed. Academic Press, p. 183–254.Google Scholar
  6. 6.
    Aberhart, D. J., J. Y. R. Chu, N. Nuess, C. H. Nash, J. Occolowitz, L. L. Huckstep, and N. DeLa Higuera. 1974. Retention of Valine Methyl Hydrogens in Penicillin Biosynthesis. J. Chem. Soc., Chem. Comm.: 564–565.Google Scholar
  7. 7.
    Archer, R. A., R. D. G. Cooper, and P. V. Demarco. 1970. Structural Studies on Penicillin Derivatives: 13C Nuclear Magnetic Resonance Studies of Some Penicillins and Related Sulfoxides. J. Chem. Soc, Chem. Comm.:1291–1293.Google Scholar
  8. 8.
    Aberhart, D. J. and L. J. Lin. 1973. Studies on the Biosynthesis of β-Lactam Antibiotics, I. Synthesis of (2RS, 3S)-[4,4,4–2H3] Valine. J. Am. Chem. Soc., 95: 7859–7860.PubMedCrossRefGoogle Scholar
  9. 9.
    Aberhart, D. J. and L. J. Lin. 1974. Studies on the Biosynthesis of β-Lactam Antibiotics, Part 1. Stereospecific Synthesis of (2RS, 3S)-[4,4,4–2H3]-,(2RS, 3S)-[4–3H]-, (3RS, 3R)-[4–3H]-, and (2RS, 3S)-[4-13C]-Valine. Incorporation of (2RS, 3S)-4-13C]-Valine into Penicillin V. J. Chem. Soc, Perkin Trans. 1:2320–2326.CrossRefGoogle Scholar
  10. 10.
    Hill, R. K., S. Yan, and S. M. Arfin. 1973. Enzymatic Discrimination between Diastereotopic Enol Faces in the Dehydrase Step of Valine Biosynthesis. J. Am. Chem. Soc. 95:7857–7859.PubMedCrossRefGoogle Scholar
  11. 11.
    Baldwin, J. E., J. Loliger, W. Rastetter, N. Nuess, L. L. Huckstep, and N. DeLa Higuera. 1973. . J. Am. Chem. Soc. 95:3796–3797.PubMedCrossRefGoogle Scholar
  12. 12.
    Nuess, N., C. H. Nash, J. E. Baldwin, P. A. Lemke, and J. B. Grutzner. 1973. Incorporation of (2RS, 3S)-[4-13C] Valine into Cephalosporin C. J. Am. Chem. Soc. 95:3797–3798.CrossRefGoogle Scholar
  13. 13.
    Kluender, H., C. H. Bradley, C. J. Sih, P. Fawcett, and E. P. Abraham. 1973. Synthesis and Incorporation of (2RS, 3S)-[4-13C] Valine into β-Lactam Antibiotics. J. Am. Chem. Soc. 95:6149–6150.CrossRefGoogle Scholar
  14. 14.
    Aberhart, D. J., L. J. Lin, and J. Y. R. Chu. 1975. Studies on the Biosynthesis of β-Lactam Antibiotics. Part II. Synthesis, and Incorporation into Penicillin G, of (2RS, 2′RS, 3R, 3′R)-[3.3′-3H2] -Cystine and (2RS, 2′RS, 3S, 3’S)-[3,3′-3H2]-Cystine. J. Chem. Soc, Perkin Trans. 1:2517–2523.CrossRefGoogle Scholar
  15. 15.
    Huddleston, J. A., E. P. Abraham, D. W. Young, D. J. Morecambe, and P. K. Sen. 1978. The Stereochemistry of β-Lactam Formation in Cephalosporin Biosynthesis. Biochem. J. 169:705–707.PubMedGoogle Scholar
  16. 16.
    Morecambe, D. J. and D. W. Young. 1975. Synthesisb of Chirally Labelled Cysteines and the Steric Origin of C(5) in Penicillin Biosynthesis. J. Chem. Soc. Chem. Comm.:198.Google Scholar
  17. 17.
    Young, D. W., D. J. Morecambe, and P. K. Sen. 1977. The Stereochemistry of β-Lactam Formation in Penicillin Biosynthesis. Eur. J. Biochem. 75:133.PubMedCrossRefGoogle Scholar
  18. 18a.
    Robinson, W. G., R. Nagle, B. K. Bachhawat, F. P. Kupiecki, and M. J. Coon. 1957. Coenzyme A Thiol Esters of Isobutyric, Methacrylic, and β-Hydroxyisobutyric Acids as Intermediates in the Enzymatic Degradation of Valine. J. Biol. Chem. 224:1–9.PubMedGoogle Scholar
  19. 18b.
    Robinson, W. G., and M. J. Coon. 1957. The Puriication and Properties of β-Hydroxyisobutyric Dehydrogenase. J. Biol. Chem. 225:511–519.PubMedGoogle Scholar
  20. 19.
    Baretz, B. and K. Tanaka. 1978. Metabolism in Rats in Vivo of Isobutyrates Labeled with Stable Isotopes at Various Positions. Identification of Propionate as an Obligate Intermediate. J. Biol. Chem. 253:4203–4213.PubMedGoogle Scholar
  21. 20.
    Tanaka, K. and I. M. Armitage. 1975. Investigaion of l3C-Valine Metabolism in Methylmalonic Acidemia Using Nuclear Magnetic Resonance: Identification of Propionate as an Obligate Inter mediate. From Proc. Second Interna Conf. Stable Isotopes. E. R. Klein and P. D. Klein, eds. National Technical Information Service, U.S. Department of Commerce, Springfield, Virginia.Google Scholar
  22. 21.
    Tanaka, K., I. M. Armitage, H. S. Ramsdell, Y. E. Hsia, S. R. Lipsky, and L. E. Rosenburg. 1975. [13c]-Valine Metabolism in Methylmalonic-acidemia Using Nuclear Magnetic Resonance: Propionate as an Obligate Intermediate. Proc. Nat. Acad. Sci. USA72:3692–3696.PubMedCrossRefGoogle Scholar
  23. 22.
    Marshall, V. P., and J. R. Sokatch. 1972. Regulation of Valine Catabolism in Pseudomonas putida. J. Bacteriol. 110:1073–1081.PubMedGoogle Scholar
  24. 23.
    Tanaka, K. Personal communication to D.J. Aberhart.Google Scholar
  25. 24.
    Aberhart, D. J. 1975. Synthesis of (2R)-[3,3,3-d3] Isobutyric Acid, Ammonium Salt. Tetrahedron Lett:4373–4374.Google Scholar
  26. 25.
    Clarke, T. G., N. A. Hampton, J. B. Lee, J. R. Morley, and B. Scanlon. 1970. Oxidations Involving Silver. Part VI. Oxidation of α-Amino-acids and α-Amino-esters with Silver(II) Picolinate and Silver(II) Oxide. J. Chem. Soc. (C): 815–817.Google Scholar
  27. 26.
    Goodhue, C. T. and J. R. Schaeffer. 1971. Prepar ation of L(+)-β-Hydroxyisobutyric Acid by Bacterial Oxidation of Isobutyric Acid. Biotechnol. Bioeng. 13:203–214.PubMedCrossRefGoogle Scholar
  28. 27.
    Aberhart, D. J. 1977. A Stereochemical Study on the Metabolism of Isobutyrate in Pseudomonas putida. Bioorg. Chem. 6: 191–201.CrossRefGoogle Scholar
  29. 28.
    Crout, D. H. G. and J. A. Corkill. 1977. Sodium Amalgam Reduction of 3-Bromopropenic Acids: A Convenient Stereoscopic Synthesis of [3–3H1] and [3–2H1] Acrylic Acids. Tetrahedron Lett: 4355–4357.Google Scholar
  30. 29.
    Willadsen, P. and H. Eggerer. 1975. Substrate Stereochemistry of the Enoyl-CoA Hydratase Reaction. Eur. J. Biochem. 54:247–252.PubMedCrossRefGoogle Scholar
  31. 30.
    Sedgwick, B., C. Morris, and S. J. French. 1978. Stereochemistry Course of Dehydration Catalysed by the Yeast Fatty Acid Synthetase. J. Chem. Soc, Chem. Comm:193–194.Google Scholar
  32. 31.
    Meister, A. 1965. Biochemistry of the Amino Acids II:729–753. Academic Press, New York.Google Scholar
  33. 32.
    Del Campillo-Campbell, A., E. E. Dekker, and M. J. Coon. 1959. Carboxylation of β-Methylcrotonyl Coenzyme A by a Purified Enzyme from Chicken Liver. Biochem. Biophys. Acta31:290–292.CrossRefGoogle Scholar
  34. 33.
    Tanaka, K. and K. J. Isselbacher. 1970. Experimental β-Hydroxyisovaleric Aciduria Induced by Biotin Deficiency. Lancet October 31:930–931.Google Scholar
  35. 34.
    Eldjarn, L., E. Jellum, O. Stokke, H. Pande, and P. E. Waaler. 1970. β-Hydroxyisovaleric Acidurea and 3-Methylacrotonylglycinuria: A New Inborn Error of Metabolism. Lancet September 5: 521–522.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • D. J. Aberhart
    • 1
  1. 1.The Worcester Foundation for Experimental BiologyShrewsburyUSA

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