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Studies on an enzyme reacting with isoniazid fromMycobacterium tuberculosis H37Rv

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Proceedings / Indian Academy of Sciences

Abstract

Mycobacterium tuberculosis H37Rv possesses an enzyme (referred to as ‘Y enzyme’) which catalyses in the presence of INH and NAD, the formation of a product, which turns yellow on acidification. The requirements for the reaction, such as enzyme concentration, INH concentration, etc., have been standardized. The substrate specificity of the enzyme with respect to INH and NAD has been determined. The reaction is specific for the INH-sensitive strain and is totally absent in INH-resistant strains. Furthermore, the ‘Y enzyme’ shows some characteristic features of a peroxidase in its requirement for oxygen and sensitivity to inhibition by various reagents. The requirements of this enzyme which is involved in the action of isoniazid inM. tuberculosis H37Rv is described for the first time.

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Abbreviations

INH:

isonicotinic acid hydrazide (isoniazid)

NAD:

nicotinamide-adenine dinucleotide

NADH:

reduced form of NAD

NADP:

nicotinamide-adenine dinucleotide phosphate

NADPH:

reduced form of NADP

NMN:

nicotinamide mononucleotide

References

  • Bernstein, J., Jambor, W. P., Lott, W. A., Pansy, F., Steinberg, B. L. and Yale, H. L., Chemotherapy of experimental tuberculosis. VI. The antituberculous activity of various carboxylic acid hydrazides, their derivatives and related compounds.Amer. Rev. Tuberc. 67 354–365 (1953).

    CAS  Google Scholar 

  • Cymerman-Craig, J., Willis, D., Rubbo, S. D. and Edgar, J., Mode of action of isonicotinic hydrazide,Nature (London) 176 34–35 (1965).

    Article  Google Scholar 

  • Gayathri Devi, B., Ramakrishnan, T. and Gopinathan, K. P., Enzymatic interaction between ioniazid and NAD.Biochem. J. 128 63 (1972).

    Google Scholar 

  • Goldman, D. S., Enzyme systems in mycobacteria—a review.Advan. Tuberc. Res. (S. Karger, Basel),11 1–44 (1961).

    Google Scholar 

  • Gopinathan, K. P., Sirsi, M. and Ramakrishnan, T., Nicotinamide adenine nucleotides ofMycobacterium tuberculosis H37Rv.Biochem. J. 87 444–448 (1963).

    PubMed  CAS  Google Scholar 

  • Gradwohl, R. B. H., inClinical Laboratory Methods and Diagnosis, Vol. 2 (C. V. Mosby & Co., St. Louis, USA). p. 1356 (1948).

    Google Scholar 

  • Honjo, T., Ikada, M., Andreoli, A. J., Nishızuka, Y. and Hayaishi, O., Enzymic preparation of nicotinate adenine dinuclotide (deamido-NAD).Biochem. Biophys. Acta 89 549–552 (1964).

    PubMed  CAS  Google Scholar 

  • Long, E. R., inChemistry and Chemotherapy of Tuberculosis, 3rd edn (The Williams and Wilkins Company, Baltimore, USA), pp. 362–388 (1958).

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J., Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193 265–275 (1951).

    PubMed  CAS  Google Scholar 

  • Ramakrishnan, T., Suryanarayana Murthy, P. and Gopinathan, K. P. Intermediary metabolism of mycobacteria.Bact. Rev. 36 65–108 (1972).

    PubMed  CAS  Google Scholar 

  • Sirsi, M. and De, N. N., Use of the mouse in experimental tuberculosis.J. Mysore Med. Assoc. 16 9–15 (1951).

    Google Scholar 

  • Sriprakash, K. S. and Ramakrishnan, T., Isoniazid resistant mutants ofMycobacterium tuberculosis H37Rv: Uptake of isoniazid and the properties of NADase inhibitor.J. Gen. Microbiol. 60 125–132 (1970).

    PubMed  CAS  Google Scholar 

  • Winder, F., The antibacterial action of streptomycin, isoniazid and PAS. InChemotherapy of Tuberculosis, ed V. C. Barry (Butterworths, London) pp. 111–149 (1964).

    Google Scholar 

  • Yale, H. L., Loses, K., Martins, J., Holsing, M., Perry, F. M. and Bernstein, J., Chemotherapy of experimental tuberculosis. VIII. The synthesis of acid hydrazides, their derivatives and related compounds.J. Amer. Chem. Soc. 75 1933–1942 (1953).

    Article  CAS  Google Scholar 

  • Youatt, J. and Tham, S. H., An enzyme system ofMycobacterium tuberculosis that specifically reacts with isoniazid.Amer. Rev. Resp. Dis. 100 25–30 (1969a).

    PubMed  CAS  Google Scholar 

  • Youatt, J. and Tham, S. H., An enzyme system ofMycobacterium tuberculosis that reacts specifically with isoniazid. II. Correlation of this reaction with the binding and metabolism of isoniazid.Amer. Rev. Resp. Dis. 100 31–37 (1969b).

    PubMed  CAS  Google Scholar 

  • Youmans, G. P. and Karlson, A. G., Streptomycin sensitivity of tubercle bacilli: Studies on recently isolated tubercle bacilli and the development of resistance to streptomycinin vivo.Amer. Rev. Tuberc. Pulmonary Dis. 55 529–534 (1947).

    Google Scholar 

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Gayathri Devi, B., Ramakrishnan, T. & Gopinathan, K.P. Studies on an enzyme reacting with isoniazid fromMycobacterium tuberculosis H37Rv. Proc. Indian Acad. Sci. 80, 240–252 (1974). https://doi.org/10.1007/BF03050671

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  • DOI: https://doi.org/10.1007/BF03050671

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