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Genetic and metabolic control of the purine catabolic enzymes of Neurospora crassa

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Neurospora crassa can utilize various purine bases such as xanthine or uric acid and their catabolic products as a nitrogen source. Four classes of mutants which affect the purine degradative pathway were isolated and studied. Mutants of the aln-1 class specifically lack allantoinase, while alc-1 mutants lack allantoicase. Mutants designated as xdh-1 cannot utilize hypoxanthine as a nitrogen source and are presumed to be deficient in xanthine dehydrogenase activity. A regulatory mutant, amr, was found to have only very low, uninduced levels of uricase, allantoinase, and allantoicase. None of these genes are closely linked to each other.

The three initial enzymes involved in the catabolism of uric acid are controlled in a complex manner by both induction and repression. Several lines of evidence indicate that the true inducer of uricase and allantoicase is uric acid. The use of the newly isolated mutant strains made it possible to demonstrate that neither allantoin nor allantoic acid could act as inducers. Furthermore, hypoxanthine itself was shown to be ineffective as an inducer although it can be metabolized to form an inducer. A non-metabolizable analogue of uric acid, 8-azaxanthine, is a gratuitous inducer of these enzymes. Uricase and allantoicase were found to be synthesized coordinately, but they were not coordinately regulated with allantoinase. Both uricase and allantoicase are stable enzymes and do not undergo turnover; nor are they subject to feedback inhibition by ammonia. Allantoinase, however, is quite labile both in vivo and in vitro. This enzyme was found to turnover in vivo in the presence of cycloheximide with a half-life of approximately 20 minutes.

The amr (for ammonia regulation) mutant cannot utilize a wide range of compounds, including purines, nitrate, and many amino acids as a nitrogen source and also displays a multiple enzyme loss. The amr gene appears to play a major role in the control of nitrogen metabolism. It is postulated that the amr locus encodes a regulatory protein which is required to activate transcription of the structural genes for a group of related enzymes involved in nitrogen metabolism.

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  1. Ames, B. N., Martin, R.: Biochemical aspects of genetics, The operon. Ann Rev. Biochem. 33, 235–258 (1964)

  2. Arst, H. N., Cove, D. J.: Nitrogen metabolite repression in Aspergillus nidulans. Molec. gen. Genet. 126, 111–141 (1973)

  3. Bergmann, F., Ungar-Waron, H., Kwientny-Govrin, H.: Action of 8-azaguanine and 8-azaxanthine on Pseudomonas aeruginosa. Biochem. J. 91, 270–276 (1964)

  4. Bollard, E. G.: A comparative study of the ability of organic nitrogenous to serve as sole sources of nitrogen for growth of plants. Plant and Soil 25, 153–166 (1966)

  5. Catcheside, D. G.: Isolation of nutritional mutants of Neurospora crassa by filtration enrichment. J. gen. Microbiol. 11, 34–36 (1954)

  6. Chaleff, R. S.: The inducible quinate-shikimate catabolic pathway in Neurospora crassa: Genetic organization. J. gen. Microbiol. 81, 337–355 (1974a)

  7. Chaleff, R. S.: The inducible quinate-shikimate catabolic pathway in Neurospora crassa: Induction and regulation of enzyme synthesis. J. gen. Microbiol. 81, 357–372 (1974b)

  8. Cooper, T. G., Lawther, R. P.: Induction of allantoin degradative enzymes in Saccharomyces cerevisiae by the last intermediate of the pathway. Proc. nat. Acad. Sci. (Wash.) 70, 2340–2344 (1973)

  9. Darlington, A. J., Scazzocchio, C., Pateman, J. A.: Biochemical and genetical studies on purine breakdown in Aspergillus. Nature (Lond.) 206, 599–600 (1965)

  10. Darlington, A. J., Scazzochio, C.: Use of analogues and the substrate-sensitivity of mutants in the analysis of purine uptake and breakdown in Aspergillus. nidulans. J. Bact. 93, 937–940 (1967)

  11. Drucker, H.: Regulation of exocellular proteases in Neurospora crassa: induction and repression of enzyme synthesis. J. Bact. 110, 1041–1049 (1972)

  12. Hanson, M. A., Marzluf, G. A.: Regulation of a sulfur-controlled protease in Neurospora crassa. J. Bact. 116, 785–789 (1973)

  13. Hanson, M. A., Marzluf, G. A.: Control of the synthesis of a single enzyme by multiple regulatory circuits in Neurospora crassa. Proc. nat. Acad. Sci. (Wash.) 72, in press (1975)

  14. Heiniger, U., Matile, Ph.: Protease secretion in Neurospora crassa. Biochem. biophys. Res. Commun. 60, 1425–1432 (1974)

  15. Kalckar, H. M.: Differential Spectrophotometry of purine compounds by means of specific enzymes. I. Determination of hydroxypurine compounds. J. biol. Chem. 167, 429–443 (1947)

  16. Ketchum, P. A., Cambier, H. Y., Frazier, W. A., Madansky, C.H., Nason, A.: In vitro assembly of Neurospora assimilatory nitrate reductase from protein subunits of a Neurospora mutant and the xanthine oxidizing or aldehyde oxidase systems of higher animals. Proc. nat. Acad. Sci. (Wash.) 66, 1016–1023 (1970)

  17. Lee, K. W., Roush, A. H.: Allantoinase assays and their application to yeast and soybean allantoinases. Arch. Biochem. Biophys. 108, 460–467 (1964)

  18. Lee, K. W., Su-Shu, P., Erickson, R., Nason, A.: Involvement of molybdenum and iron in the in vitro assembly of assimilatory nitrate reductase utilizing Neurospora mutant nit-1. J. biol. Chem. 249, 3941–3952 (1974)

  19. Marzluf, G. A., Metzenberg, R. L.: Positive control by the cys-3 locus in regulation of sulfur metabolism in Neurospora. J. molec. Biol. 33, 423–437 (1968)

  20. Metzenberg, R. L.: Genetic regulatory systems in Neurospora. Ann. Rev. Genet. 6, 111–132 (1972)

  21. North, M. J.: Cold-induced increase of glycerol kinase activity in Neurospora crassa: Rapid inactivation of the enzyme in vivo. J. Bact. 120, 741–747 (1974)

  22. Palleroni, N. J., Stanier, R. J.: Regulatory mechanisms governing synthesis of enzymes for tryptophan oxidation by Pseudomonas fluorescens. J. gen. Microbiol. 35, 319–334 (1964)

  23. Pateman, J. A., Cove, D. J., Revers, B. M., Roberts, D. B.: A common cofactor for nitrate reductase and xanthine dehydrogenase which also regulates the synthesis of nitrate reductase. Nature (Lond.) 201, 58–60 (1964)

  24. Reinert, W. R., Marzluf, G. A.: Regulation of the purine catabolic enzymes in Neurospora crassa. Arch. Biochem. Biophys. 166, 565–574 (1975)

  25. Scazzocchio, C., Darlington, A. J.: The induction and repression of the enzymes of purine breakdown in Aspergillus nidulans. Biochim. biophys. Acta (Amst. 166, 557–568 (1968)

  26. Scazzocchio, C., Holl, F. B., Foguelman, A. I.: The genetic control of molybdoflavoproteins in Aspergillus nidulans. Purinol-resistant mutants constitutive for xanthine dehydrogenase. Europ. J. Biochem. 36, 428–445 (1973)

  27. Sorger, G. J., Debanne, M. T., Davies, J.: Effect of nitrate on the synthesis and decay of nitrate reductase of Neurospora. Biochem. J. 140, 395–403 (1974)

  28. Sorger, G. J., Giles, N. H.: Genetic control of nitrate reductase in Neurospora crassa. Genetics 52, 777–788 (1965)

  29. Stevenson, I. L., Mandelstan, J.: Induction and multi-sensitive endproduct repression in two converging pathways degrading aromatic substances in Pseudomonas fluorescens. Biochem. J. 96, 354–362 (1965)

  30. Subramanian, K. N., Sorger, G. J.: Regulation of nitrate reductase in Neurospora crassa. Stability in vivo. J. Bact. 110, 538–546 (1972)

  31. Yu, P. H., Kula, M. R., Tsai, H.: Studies on the apparent instability of Neurospora tryptophan synthase. Evidence for protease. Europ. J. Biochem. 32, 129–135 (1973)

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Communicated by F. Kaudewitz

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Reinert, W.R., Marzluf, G.A. Genetic and metabolic control of the purine catabolic enzymes of Neurospora crassa . Molec. Gen. Genet. 139, 39–55 (1975). https://doi.org/10.1007/BF00267994

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  • Uric Acid
  • Nitrogen Source
  • Purine
  • Xanthine
  • Hypoxanthine